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Guo C, He Y, Shi Z, Wang L. Combined hepatocellular-cholangiocarcinoma in a middle-aged patient: A case report and review of therapeutic approaches. Int J Surg Case Rep 2025; 129:111165. [PMID: 40106944 PMCID: PMC11964574 DOI: 10.1016/j.ijscr.2025.111165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 03/11/2025] [Accepted: 03/15/2025] [Indexed: 03/22/2025] Open
Abstract
INTRODUCTION Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a rare hepatic malignancy featuring both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) components, often leading to poor prognosis owing to its clinical complexity. CASE PRESENTATION A middle-aged man presented with sudden abdominal pain and unexplained weight loss, leading to an initial diagnosis of CCA. The patient underwent laparoscopic left hepatectomy and lymph node dissection, and postoperative pathology confirmed cHCC-CCA with lymph node metastasis. Despite initial recovery, the disease recurred at 2 months and progressed to lung metastasis and multi-organ involvement by 7 months. Immuno-combination targeted therapy was ineffective, and the patient succumbed to the disease eight months after surgery. DISCUSSION This case highlights the diagnostic and therapeutic challenges of cHCC-CCA, including its histological complexity, high recurrence rate, and limited treatment efficacy. Despite surgical resection, early recurrence and rapid progression to pulmonary metastasis were observed, emphasizing the need for improved treatment strategies for this condition. The failure of immune checkpoint inhibitors and targeted therapy suggests the need for alternative or combined therapeutic approaches. CONCLUSION Future research should focus on integrating molecular profiling into treatment selection, optimizing adjuvant therapies, and exploring novel targeted or immunotherapy combinations to improve the long-term outcomes. This report contributes to the growing evidence on cHCC-CCA and underscores the urgency of developing precise diagnostic tools and personalized treatment strategies.
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Affiliation(s)
- Chen Guo
- The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China
| | - Yutao He
- The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China
| | - Zhitian Shi
- The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China
| | - Lin Wang
- The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China.
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Nolasco F, Fonseca GM, de Mello ES, Kruger JAP, Jeismann VB, Makdissi FF, Coelho FF, Alves VAF, Herman P. Prognostic Impact of the Cholangiolar Component in Combined Hepatocellular-Cholangiocarcinoma: Insights From a Western Single-Center Study. J Surg Oncol 2025; 131:427-434. [PMID: 39410740 DOI: 10.1002/jso.27955] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 09/23/2024] [Accepted: 10/02/2024] [Indexed: 05/02/2025]
Abstract
INTRODUCTION Primary liver malignancies, such as hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined hepatocellular-cholangiocarcinoma (cHCC-CCA), represent significant contributors to global cancer-related mortality. The diagnostic challenges associated with distinguishing cHCC-CCA from HCC and ICC stem from their rarity and overlapping histological features. OBJECTIVES This study aimed to reclassify primary liver tumors resected at a Western center and to compare clinicopathological features and prognosis among patients with HCC, ICC, and cHCC-CCA. METHODS A retrospective analysis was conducted on patients undergoing resection for HCC, ICC, or cHCC-CCA between 2007 and 2017. Clinical and perioperative data were collected, and pathological specimens were reclassified by a specialized pathologist. Statistical analysis was employed to compare clinical features and survival outcomes among the different tumor types. RESULTS Out of the initially identified 192 patients, 140 were included in the analysis. Following reclassification, 71.42% were diagnosed with HCC, 12.14% with ICC, and 16.42% with cHCC-CCA. Patients with HCC were predominantly male and exhibited a higher incidence of isolated liver recurrence. ICC patients more frequently underwent open procedures. Additionally, patients with HCC and cHCC-CCA showed higher rates of cirrhosis, elevated alpha-fetoprotein levels, and extrahepatic recurrence, while those with ICC and cHCC-CCA demonstrated elevated CA 19-9 levels. Overall survival and disease-free survival were longer for HCC compared to cases with a cholangiolar component (ICC and cHCC-CCA). CONCLUSIONS Histological evaluation should actively incorporate the search for a cholangiolar component in primary liver tumors to prevent misdiagnosis, as its presence indicates a poorer prognosis.
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Affiliation(s)
- Francisco Nolasco
- Liver Surgery Unit, Department of Gastroenterology, Digestive Surgery Division, University of Saão Paulo Medical School, São Paulo, Brazil
| | - Gilton Marques Fonseca
- Liver Surgery Unit, Department of Gastroenterology, Digestive Surgery Division, University of Saão Paulo Medical School, São Paulo, Brazil
| | - Evandro S de Mello
- Departament of Pathology, University of São Paulo Medical School, São Paulo, Brazil
| | - Jaime Arthur Pirolla Kruger
- Liver Surgery Unit, Department of Gastroenterology, Digestive Surgery Division, University of Saão Paulo Medical School, São Paulo, Brazil
| | - Vagner Birk Jeismann
- Liver Surgery Unit, Department of Gastroenterology, Digestive Surgery Division, University of Saão Paulo Medical School, São Paulo, Brazil
| | - Fabio Ferrari Makdissi
- Liver Surgery Unit, Department of Gastroenterology, Digestive Surgery Division, University of Saão Paulo Medical School, São Paulo, Brazil
| | - Fabricio Ferreira Coelho
- Liver Surgery Unit, Department of Gastroenterology, Digestive Surgery Division, University of Saão Paulo Medical School, São Paulo, Brazil
| | - Venancio A F Alves
- Departament of Pathology, University of São Paulo Medical School, São Paulo, Brazil
| | - Paulo Herman
- Liver Surgery Unit, Department of Gastroenterology, Digestive Surgery Division, University of Saão Paulo Medical School, São Paulo, Brazil
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Chun SJ, Jung YJ, Choi Y, Yi NJ, Lee KW, Suh KS, Lee KB, Kang HC, Chie EK, Kim KS. Prognostic Evaluation and Survival Prediction for Combined Hepatocellular-Cholangiocarcinoma Following Hepatectomy. Cancer Res Treat 2025; 57:229-239. [PMID: 38965925 PMCID: PMC11729305 DOI: 10.4143/crt.2024.176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Accepted: 06/26/2024] [Indexed: 07/06/2024] Open
Abstract
PURPOSE This study aimed to assess prognostic factors associated with combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and to predict 5-year survival based on these factors. MATERIALS AND METHODS Patients who underwent definitive hepatectomy from 2006 to 2022 at a single institution was retrospectively analyzed. Inclusion criteria involved a pathologically confirmed diagnosis of cHCC-CCA. RESULTS A total of 80 patients with diagnosed cHCC-CCA were included in the analysis. The median progression-free survival was 15.6 months, while distant metastasis-free survival (DMFS), hepatic progression-free survival, and overall survival (OS) were 50.8, 21.5, and 85.1 months, respectively. In 52 cases of recurrence, intrahepatic recurrence was the most common initial recurrence (34/52), with distant metastasis in 17 cases. Factors associated with poor DMFS included tumor necrosis, lymphovascular invasion (LVI), perineural invasion, and histologic compact type. Postoperative carbohydrate antigen 19-9, tumor necrosis, LVI, and close/positive margin were associated with poor OS. LVI emerged as a key factor affecting both DMFS and OS, with a 5-year OS of 93.3% for patients without LVI compared to 35.8% with LVI. Based on these factors, a nomogram predicting 3-year and 5-year DMFS and OS was developed, demonstrating high concordance with actual survival in the cohort (Harrell C-index 0.809 for OS, 0.801 for DMFS, respectively). CONCLUSION The prognosis of cHCC-CCA is notably poor when combined with LVI. Given the significant impact of adverse features, accurate outcome prediction is crucial. Moreover, consideration of adjuvant therapy may be warranted for patients exhibiting poor survival and increased risk of local recurrence or distant metastasis.
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Affiliation(s)
- Seok-Joo Chun
- Department of Radiation Oncology, Seoul National University Hospital, Seoul, Korea
- Department of Radiation Oncology, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Korea
| | - Yu Jung Jung
- Department of Radiation Oncology, Seoul National University Hospital, Seoul, Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Hospital, Seoul, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University Hospital, Seoul, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University Hospital, Seoul, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kyoung Bun Lee
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
| | - Hyun-Cheol Kang
- Department of Radiation Oncology, Seoul National University Hospital, Seoul, Korea
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea
| | - Eui Kyu Chie
- Department of Radiation Oncology, Seoul National University Hospital, Seoul, Korea
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung Su Kim
- Department of Radiation Oncology, Seoul National University Hospital, Seoul, Korea
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea
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Zhu Z, Yang C, Zeng M, Zhou C. Prognostic Impact of CCA Components in Combined Hepatocellular Carcinoma-Cholangiocarcinoma. J Hepatocell Carcinoma 2024; 11:2483-2492. [PMID: 39712948 PMCID: PMC11663380 DOI: 10.2147/jhc.s491243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Accepted: 12/14/2024] [Indexed: 12/24/2024] Open
Abstract
Purpose To investigate the differences of combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) patients with a cholangiocarcinoma (CCA) component ≥ 30% or < 30% versus intrahepatic cholangiocarcinoma (iCCA) patients in recurrence-free survival (RFS) and overall survival (OS) prognoses. Methods Patients with cHCC-CCA and iCCA after surgery were recruited. All cHCC-CCA patients were divided into two subgroups (CCA components ≥ 30% and < 30%). Then, Kaplan-Meier survival analysis and Cox regression analysis were used to investigate and compare the differences of cHCC-CCAs with a CCA component ≥ 30% or < 30% versus iCCAs in RFS and OS prognoses, respectively. The differences of MRI features between cHCC-CCAs with a CCA component ≥ 30% and < 30% were also compared. Results One hundred sixty-four cHCC-CCAs and 146 iCCAs were enrolled. Compared with iCCAs, cHCC-CCAs with a CCA component < 30% had better OS prognosis (HR: 2.888, p = 0.045). However, Cox regression analysis revealed that cHCC-CCAs with a CCA component ≥ 30% had poorer RFS (HR: 0.503, p < 0.001) and OS (HR: 0.58, p = 0.033) prognoses than iCCAs. In addition, rim APHE (OR = 0.286, p < 0.001), targetoid diffusion restriction (OR = 0.316, p = 0.019), corona enhancement (OR = 0.481, p = 0.033), delayed enhancement (OR = 0.251, p = 0.001), and LR-M (OR = 1.586, p < 0.001) were significant factors associated with cHCC-CCAs with a CCA component ≥ 30%. Multivariable regression analyses showed that only LR-M (OR = 1.522, p = 0.042) was a significantly independent predictor for cHCC-CCAs with a CCA component ≥ 30%. Conclusion cHCC-CCAs with a CCA component ≥ 30% had worse prognoses than iCCAs. Therefore, we suggest that the postoperative treatment of cHCC-CCAs with a CCA component ≥ 30% can be based on the treatment strategy for iCCAs.
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Affiliation(s)
- Zhu Zhu
- Department of Radiology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, People’s Republic of China
| | - Chun Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Changwu Zhou
- Department of Radiology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, People’s Republic of China
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Lin RY, Kahramangil D, Ozer M, George TJ, Nassour I, Hughes SJ, Zarrinpar A, Sahin I. Patient Outcomes in Resected Combined Hepatocellular Cholangiocarcinoma (cHCC-ICC) and Intrahepatic Cholangiocarcinoma: A Single Center Study. Cancers (Basel) 2024; 16:3878. [PMID: 39594833 PMCID: PMC11592994 DOI: 10.3390/cancers16223878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 11/16/2024] [Accepted: 11/18/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND/OBJECTIVES Combined hepatocellular cholangiocarcinoma (cHCC-ICC) is a rare malignancy that involves a combination of features of hepatocellular carcinoma and intrahepatic cholangiocarcinoma (ICC) and exhibits a more aggressive clinical course; however, its risk factors and outcomes remain largely undefined. METHODS This study is a single-center retrospective study of 82 patients diagnosed with ICC or cHCC-ICC who underwent surgical resection from June 2011 to January 2023. Our analysis included 70 patients with resected ICC and 12 with resected cHCC-ICC. RESULTS The overall survival (OS) for the entire cohort was 21.6 months, with a recurrence-free survival (RFS) of 11.8 months. The cHCC-ICC group had significantly higher levels of AST and ALT (AST median 206 U/L vs. 46 U/L; ALT median 165.5 U/L vs. 48 U/L; p = 0.012 and p = 0.013, respectively), whereas the ICC group had higher alkaline phosphatase (median 66 U/L vs. 104 U/L; p = 0.03). CA 19-9 values (76 U/mL vs. 22 U/mL; p = 0.02) were higher in the ICC group, while AFP values were higher in the cHCC-ICC group (7.3 ng/mL vs. 3.2 ng/mL; p = 0.0004). The cHCC-ICC group had a significantly higher rate of recurrence (83% vs. 47%, p = 0.028) with a significantly decreased RFS (4.7 months vs. 12.4 months; log-rank p = 0.007). In multivariate analysis, patients with resected ICC had a significantly reduced risk of recurrence by 73% compared to their counterparts (HR 0.27 [0.10-0.73], p = 0.01). CONCLUSIONS cHCC-ICC is a rare entity that needs to be further studied to improve patient outcomes. Further studies are warranted and may suggest the need for more aggressive initial treatment strategies in patients diagnosed with cHCC-ICC.
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Affiliation(s)
- Rick Y. Lin
- Department of Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA;
| | - Doga Kahramangil
- Department of Medicine, Division of Hematology and Oncology, College of Medicine, University of Florida, Gainesville, FL 32610, USA; (D.K.); (T.J.G.)
| | - Muhammet Ozer
- Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA;
| | - Thomas J. George
- Department of Medicine, Division of Hematology and Oncology, College of Medicine, University of Florida, Gainesville, FL 32610, USA; (D.K.); (T.J.G.)
| | - Ibrahim Nassour
- Department of Surgery, University of Florida, Gainesville, FL 32610, USA; (I.N.); (S.J.H.); (A.Z.)
| | - Steven J. Hughes
- Department of Surgery, University of Florida, Gainesville, FL 32610, USA; (I.N.); (S.J.H.); (A.Z.)
| | - Ali Zarrinpar
- Department of Surgery, University of Florida, Gainesville, FL 32610, USA; (I.N.); (S.J.H.); (A.Z.)
| | - Ilyas Sahin
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
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Zhou C, Yang C, Zeng M. Is it necessary to distinguish between combined hepatocellular carcinoma-cholangiocarcinoma with less than 10% of cholangiocarcinoma components versus hepatocellular carcinoma? Hepatol Int 2024:10.1007/s12072-024-10730-1. [PMID: 39298106 DOI: 10.1007/s12072-024-10730-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Accepted: 09/06/2024] [Indexed: 09/21/2024]
Abstract
PURPOSE Whether there are differences in recurrence-free survival (RFS) prognosis between combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) cases with a small proportion of CCA components and HCC cases remains unknown. We aim to investigate the differences in RFS prognosis between cHCC-CCAs with a small proportion of CCA components and HCCs. METHODS Patients with malignant liver neoplasms who underwent MRI and surgery were prospectively recruited. All cHCC-CCA patients were divided into different groups according to the ratio of CCA components. The primary end point was recurrence-free-survival. Cox regression analysis and Kaplan-Meier survival analysis was used to investigate and compare RFS prognosis. RESULTS One hundred sixty-four cHCC-CCA cases and 271 HCC cases were enrolled. There was no significant difference in RFS prognosis between cHCC-CCA cases with a CCA component of < 10% and HCC cases (log rank p = 0.169). There were no significant differences in some major HCC-favoring MR features, such as nonrim APHE (85.7% vs. 81.5%, p = 0.546), nonperipheral washout (80.0% vs. 84.1%, p = 0.534), and enhancing capsule (62.9% vs. 45.4%, p = 0.051) between them. In addition, some clinicopathological findings had no significant differences between cHCC-CCAs with a CCA component of < 10% and HCCs (all p > 0.05). CONCLUSIONS There were no significant differences in RFS prognosis, major HCC-favoring MRI features, and clinicopathological findings between cHCC-CCAs with a CCA component of < 10% and HCCs. Therefore, we suggest that cHCC-CCAs with pathological diagnosis of less than 10% of CCA components may be treated as HCCs in clinical setting.
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Affiliation(s)
- Changwu Zhou
- Department of Radiology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Chun Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
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Gong W, Zhang S, Tian X, Chen W, He Y, Chen L, Ding T, Ren P, Shi L, Wu Q, Sun Y, Chen L, Guo H. Tertiary lymphoid structures as a potential prognostic biomarker for combined hepatocellular-cholangiocarcinoma. Hepatol Int 2024; 18:1310-1325. [PMID: 38767772 PMCID: PMC11297834 DOI: 10.1007/s12072-024-10694-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Accepted: 04/24/2024] [Indexed: 05/22/2024]
Abstract
BACKGROUND Combined hepatocellular-cholangiocarcinoma (cHCC-CCA), as a rare primary hepatic tumor, is challenging to accurately assess in terms of the clinical outcomes and prognostic risk factors in patients. This study aimed to clarify the function of tertiary lymphoid structure (TLS) status in predicting the outcome of cHCC-CCA and to preliminarily explore the possible mechanism of TLS formation. METHODS The TLSs, with different spatial distributions and densities, of 137 cHCC-CCA were quantified, and their association with prognosis was assessed by Cox regression and Kaplan-Meier analyses. We further validated TLS possible efficacy in predicting immunotherapy responsiveness in two cHCC-CCA case reports. TLS composition and its relationship to CXCL12 expression were analysed by fluorescent multiplex immunohistochemistry. RESULTS A high intratumoural TLS score was correlated with prolonged survival, whereas a high TLS density in adjacent tissue indicated a worse prognosis in cHCC-CCA. Mature TLSs were related to favorable outcomes and showed more CD8 + T cells infiltrating tumor tissues. We further divided the cHCC-CCA patients into four immune grades by combining the peri-TLS and intra-TLS, and these grades were an independent prognostic factor. In addition, our reported cases suggested a potential value of TLS in predicting immunotherapy response in cHCC-CCA patients. Our findings suggested that CXCL12 expression in cHCC-CCA tissue was significantly correlated with TLS presence. CONCLUSION The spatial distribution and density of TLSs revealing the characteristics of the cHCC-CCA immune microenvironment, significantly correlated with prognosis and provided a potential immunotherapy response biomarker for cHCC-CCA.
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Affiliation(s)
- Wenchen Gong
- Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China
- National Clinical Research Center for Cancer, National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Su Zhang
- Department of Gynecological Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China
- National Clinical Research Center for Cancer, National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Xiangdong Tian
- Department of Endoscopic Diagnosis and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China
- National Clinical Research Center for Cancer, National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Wenshuai Chen
- Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China
- National Clinical Research Center for Cancer, National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Yuchao He
- Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China
- National Clinical Research Center for Cancer, National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Liwei Chen
- Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China
- National Clinical Research Center for Cancer, National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Tingting Ding
- Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China
- National Clinical Research Center for Cancer, National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Peiqi Ren
- Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China
- National Clinical Research Center for Cancer, National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Lin Shi
- Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China
- National Clinical Research Center for Cancer, National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Qiang Wu
- Department of Hepatobiliary Cancer, Tianjin Medical University Cancer Institute and Hospital, Liver Cancer Research Center, Tianjin, 300060, China.
- National Clinical Research Center for Cancer, National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.
| | - Yan Sun
- Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
- National Clinical Research Center for Cancer, National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.
| | - Lu Chen
- Department of Hepatobiliary Cancer, Tianjin Medical University Cancer Institute and Hospital, Liver Cancer Research Center, Tianjin, 300060, China.
- National Center for Global Health and Medicine, Department of Hepato-Biliary-Pancreatic Surgery, Tokyo, Japan.
- National Clinical Research Center for Cancer, National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.
| | - Hua Guo
- Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
- National Clinical Research Center for Cancer, National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.
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Gurzu S, Szodorai R, Jung I, Banias L. Combined hepatocellular-cholangiocarcinoma: from genesis to molecular pathways and therapeutic strategies. J Cancer Res Clin Oncol 2024; 150:270. [PMID: 38780656 PMCID: PMC11116183 DOI: 10.1007/s00432-024-05781-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Accepted: 05/04/2024] [Indexed: 05/25/2024]
Abstract
Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common primary liver cancers. Little is known about the combined hepatocellular-cholangiocarcinoma (cHCC-ICC) variant and the proper therapeutic strategies. Out of over 1200 available studies about cHCC-ICC, we selected the most representative ones that reflected updated information with application to individualized therapy. Based on literature data and own experience, we hypothesize that two molecular groups of cHCC-ICC can be identified. The proposed division might have a significant therapeutic role. Most cases develop, like HCC, on a background of cirrhosis and hepatitis and share characteristics with HCC; thus, they are named HCC-type cHCC-ICC and therapeutic strategies might be like those for HCC. This review also highlights a new carcinogenic perspective and identifies, based on literature data and the own experience, a second variant of cHCC-ICC called ICC-type cHCC-ICC. Contrary to HCC, these cases show a tendency for lymph node metastases and ICC components in the metastatic tissues. No guidelines have been established yet for such cases. Individualized therapy should be, however, oriented toward the immunoprofile of the primary tumor and metastatic cells, and different therapeutic strategies should be used in patients with HCC- versus ICC-type cHCC-ICC.
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Affiliation(s)
- Simona Gurzu
- Department of Pathology, Pharmacy, Science and Technology, George Emil Palade University of Medicine, 38 Gheorghe Marinescu Street, 540139, Targu Mures, Romania.
- Research Center of Oncopathology and Transdisciplinary Research (CCOMT), Targu Mures, Romania.
- Romanian Academy of Medical Sciences, Bucharest, Romania.
| | - Rita Szodorai
- Department of Pathology, Pharmacy, Science and Technology, George Emil Palade University of Medicine, 38 Gheorghe Marinescu Street, 540139, Targu Mures, Romania
| | - Ioan Jung
- Department of Pathology, Pharmacy, Science and Technology, George Emil Palade University of Medicine, 38 Gheorghe Marinescu Street, 540139, Targu Mures, Romania
- Romanian Academy of Medical Sciences, Bucharest, Romania
| | - Laura Banias
- Department of Pathology, Pharmacy, Science and Technology, George Emil Palade University of Medicine, 38 Gheorghe Marinescu Street, 540139, Targu Mures, Romania
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Haghshomar M, Rodrigues D, Kalyan A, Velichko Y, Borhani A. Leveraging radiomics and AI for precision diagnosis and prognostication of liver malignancies. Front Oncol 2024; 14:1362737. [PMID: 38779098 PMCID: PMC11109422 DOI: 10.3389/fonc.2024.1362737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 04/12/2024] [Indexed: 05/25/2024] Open
Abstract
Liver tumors, whether primary or metastatic, have emerged as a growing concern with substantial global health implications. Timely identification and characterization of liver tumors are pivotal factors in order to provide optimum treatment. Imaging is a crucial part of the detection of liver tumors; however, conventional imaging has shortcomings in the proper characterization of these tumors which leads to the need for tissue biopsy. Artificial intelligence (AI) and radiomics have recently emerged as investigational opportunities with the potential to enhance the detection and characterization of liver lesions. These advancements offer opportunities for better diagnostic accuracy, prognostication, and thereby improving patient care. In particular, these techniques have the potential to predict the histopathology, genotype, and immunophenotype of tumors based on imaging data, hence providing guidance for personalized treatment of such tumors. In this review, we outline the progression and potential of AI in the field of liver oncology imaging, specifically emphasizing manual radiomic techniques and deep learning-based representations. We discuss how these tools can aid in clinical decision-making challenges. These challenges encompass a broad range of tasks, from prognosticating patient outcomes, differentiating benign treatment-related factors and actual disease progression, recognizing uncommon response patterns, and even predicting the genetic and molecular characteristics of the tumors. Lastly, we discuss the pitfalls, technical limitations and future direction of these AI-based techniques.
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Affiliation(s)
| | | | | | | | - Amir Borhani
- Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
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10
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Zhang YZ, Liu YC, Su T, Shi JN, Huang Y, Liang B. Current advances and future directions in combined hepatocellular and cholangiocarcinoma. Gastroenterol Rep (Oxf) 2024; 12:goae031. [PMID: 38628397 PMCID: PMC11018545 DOI: 10.1093/gastro/goae031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 03/17/2024] [Accepted: 03/24/2024] [Indexed: 04/19/2024] Open
Abstract
The low incidence of combined hepatocellular cholangiocarcinoma (cHCC-CCA) is an important factor limiting research progression. Our study extensively included nearly three decades of relevant literature and assembled the most comprehensive database comprising 5,742 patients with cHCC-CCA. We summarized the characteristics, tumor markers, and clinical features of these patients. Additionally, we present the evolution of cHCC-CCA classification and explain the underlying rationale for these classification standards. We reviewed cHCC-CCA diagnostic advances using imaging features, tumor markers, and postoperative pathology, as well as treatment options such as surgical, adjuvant, and immune-targeted therapies. In addition, recent advances in more effective chemotherapeutic regimens and immune-targeted therapies were explored. Furthermore, we described the molecular mutation features and potential specific markers of cHCC-CCA. The prognostic value of Nestin has been proven, and we speculate that Nestin will also play a role in classification and diagnosis. However, further research is needed. Moreover, we believe that the possibility of using machine learning liquid biopsy for preoperative diagnosis and establishing a scoring system are directions for future research.
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Affiliation(s)
- Yu-Zhu Zhang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, Jiangxi, P. R. China
- The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, Jiangxi, P. R. China
| | - Yu-Chen Liu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, Jiangxi, P. R. China
- Queen Mary School, Jiangxi Medical College of Nanchang University, Nanchang, Jiangxi, P. R. China
| | - Tong Su
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, Jiangxi, P. R. China
- The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, Jiangxi, P. R. China
| | - Jiang-Nan Shi
- The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, Jiangxi, P. R. China
| | - Yi Huang
- The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, Jiangxi, P. R. China
| | - Bo Liang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, Jiangxi, P. R. China
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11
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Khessairi N, Mallek I, Laabidi T, Lahmar A, Bacha D, Slama SB. Synchronous presentation of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: Report of an exceptional case with review of the literature. Int J Surg Case Rep 2024; 114:109140. [PMID: 38113560 PMCID: PMC10767223 DOI: 10.1016/j.ijscr.2023.109140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 12/05/2023] [Accepted: 12/06/2023] [Indexed: 12/21/2023] Open
Abstract
INTRODUCTION AND IMPORTANCE The occurrence of distinct synchronous hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (CC) is extremely rare. Less than 50 cases have been reported in the literature. The aim of our study was to describe the clinicopathological features of this association. CASE PRESENTATION A 75-year-old female patient with chronic hepatitis C cirrhosis presented with three hepatic nodules affecting segments IV, VIII and V during follow-up of her disease. Only the V-segment nodule was radiologically suspicious of malignancy (classified as LI-RADS5). These nodules were resected after discussion of the case in a multidisciplinary meeting. Histological examination showed that the nodules in segments VIII and V corresponded respectively to an HCC with immunohistochemistry showing HepPar1 (+), CK7(-) and CK19(-), and to an intrahepatic CC with immunohistochemistry showing HepPar1 (-), CK7(+) and CK19(+). The excision was radical. The post-operative course was uncomplicated. After a 6-month follow-up, the patient did not develop any locoregional recurrence or metastases. CLINICAL DISCUSSION Synchronous association of HCC and CC is very uncommon, and diagnosis is based on pathological and immunohistochemical examination. Infection with the HCV represents a major risk factor for simultaneous association. Synchronous presentation in HCV-infected individuals has been associated with a poorer prognosis compared with cases where only a single type of liver cancer is present. CONCLUSION The prognosis of this association is generally poor, notably due to the aggressive behavior of CC. Surgical resection remains the first-line treatment option, when possible, but comprehensive management of these complex cases requires a multidisciplinary approach tailored to each patient's specific circumstances.
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Affiliation(s)
- Nayssem Khessairi
- Department of Pathology, M. Slim University Hospital Center, Tunisia.
| | - Inès Mallek
- Department of Pathology, M. Slim University Hospital Center, Tunisia
| | - Taher Laabidi
- Department of Surgery, M. Slim University Hospital Center, Tunisia
| | - Ahlem Lahmar
- Department of Pathology, M. Slim University Hospital Center, Tunisia; University of Tunis El Manar, Faculty of Medicine of Tunis, Tunisia
| | - Dhouha Bacha
- Department of Pathology, M. Slim University Hospital Center, Tunisia; University of Tunis El Manar, Faculty of Medicine of Tunis, Tunisia
| | - Sana Ben Slama
- Department of Pathology, M. Slim University Hospital Center, Tunisia; University of Tunis El Manar, Faculty of Medicine of Tunis, Tunisia
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12
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Chen J, Zhang W, Bao J, Wang K, Zhao Q, Zhu Y, Chen Y. Implications of ultrasound-based deep learning model for preoperatively differentiating combined hepatocellular-cholangiocarcinoma from hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Abdom Radiol (NY) 2024; 49:93-102. [PMID: 37999743 DOI: 10.1007/s00261-023-04089-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 10/08/2023] [Accepted: 10/09/2023] [Indexed: 11/25/2023]
Abstract
OBJECTIVES The current study developed an ultrasound-based deep learning model to make preoperative differentiation among hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined hepatocellular-cholangiocarcinoma (cHCC-ICC). METHODS The B-mode ultrasound images of 465 patients with primary liver cancer were enrolled in model construction, comprising 264 HCCs, 105 ICCs, and 96 cHCC-ICCs, of which 50 cases were randomly selected to form an independent test cohort, and the rest of study population was assigned to a training and validation cohorts at the ratio of 4:1. Four deep learning models (Resnet18, MobileNet, DenseNet121, and Inception V3) were constructed, and the fivefold cross-validation was adopted to train and validate the performance of these models. The following indexes were calculated to determine the differential diagnosis performance of the models, including sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), F-1 score, and area under the receiver operating characteristic curve (AUC) based on images in the independent test cohort. RESULTS Based on the fivefold cross-validation, the Resnet18 outperformed other models in terms of accuracy and robustness, with the overall training and validation accuracy as 99.73% (± 0.07%) and 99.35% (± 0.53%), respectively. Furthers validation based on the independent test cohort suggested that Resnet 18 yielded the best diagnostic performance in identifying HCC, ICC, and cHCC-ICC, with the sensitivity, specificity, accuracy, PPV, NPV, F1-score, and AUC of 84.59%, 92.65%, 86.00%, 85.82%, 92.99%, 92.37%, 85.07%, and 0.9237 (95% CI 0.8633, 0.9840). CONCLUSION Ultrasound-based deep learning algorithm appeared a promising diagnostic method for identifying cHCC-ICC, HCC, and ICC, which might play a role in clinical decision making and evaluation of prognosis.
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Affiliation(s)
- Jianan Chen
- The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Weibin Zhang
- Department of Ultrasound, Huashan Hospital, Fudan University, Shanghai, China
| | - Jingwen Bao
- School of Medical Science, Hexi University, Zhangye, China
| | - Kun Wang
- Department of Ultrasound, The Affiliated Hospital of Binzhou Medical University, Binzhou, China
| | - Qiannan Zhao
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yuli Zhu
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China.
| | - Yanling Chen
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China.
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13
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Lv TR, Hu HJ, Ma WJ, Liu F, Jin YW, Li FY. Meta-analysis of prognostic factors for overall survival and disease-free survival among resected patients with combined hepatocellular carcinoma and cholangiocarcinoma. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:107279. [PMID: 38000116 DOI: 10.1016/j.ejso.2023.107279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 11/09/2023] [Accepted: 11/15/2023] [Indexed: 11/26/2023]
Abstract
BACKGROUND Combined hepatocellular carcinoma and cholangiocarcinoma (CHCC-CC) is a rare subtype of primary liver malignancy and has been treated equally as intra-hepatic cholangiocarcinoma (IHCC) according to the 8th AJCC staging system. Owing to its rarity, its prognostic factors have been rarely explored and defined. METHODS PubMed, EMBASE, the Cochrane Library and Web of Science were searched up till January 1st, 2023 and eligible studies were restricted to studies reported prognostic factors of resected CHCC-CC. Standard Parmar modifications were used to determine pooled univariable hazard ratios (HRs). RESULTS A total of eleven studies with 1286 patients with resected classical CHCC-CC were finally included. Pooled results indicated that serum tumor biomarkers, including AFP, CA199, and CEA, were prognostic factors for postoperative overall survival (OS) and disease-free survival (DFS). Moreover, liver cirrhosis (P = 0.010), HBV infection (P = 0.030), and HCV infection (P < 0.001) were prognostic factors for OS. Age (HR = 1.03, P = 0.005) was a prognostic factor for DFS. Tumor size (OS: HR = 2, P < 0.001, DFS: HR = 2.15, P < 0.001), tumor number (OS: HR = 2.05, P < 0.001; DFS: HR = 1.96, P = 0.006), surgical margin (OS: HR = 2.33, <0.001001; DFS: HR = 2.35, P < 0.001), node metastasis (OS: HR = 2.96, P < 0.001; DFS: HR = 2.1, P < 0.001), vascular invasion (OS: HR = 2.17, P < 0.001; DFS: HR = 2.64, P < 0.001), and postoperative prophylactic trans-arterial chemotherapy embolization (PPTACE) (OS: HR = 1.67, P = 0.04; DFS: HR = 2.31, P < 0.001) were common prognostic factors for OS and DFS. CONCLUSION Various risk factors unmentioned in the 8th AJCC staging system were identified. These promising findings would facilitate a more personalized predictive model and help clinicians to stratify patients with different survival outcomes.
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Affiliation(s)
- Tian-Run Lv
- Department of Biliary Tract Surgery, General Surgrey, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Hai-Jie Hu
- Department of Biliary Tract Surgery, General Surgrey, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Wen-Jie Ma
- Department of Biliary Tract Surgery, General Surgrey, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Fei Liu
- Department of Biliary Tract Surgery, General Surgrey, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Yan-Wen Jin
- Department of Biliary Tract Surgery, General Surgrey, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Fu-Yu Li
- Department of Biliary Tract Surgery, General Surgrey, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.
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14
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Kim J, Joo DJ, Hwang S, Lee JM, Ryu JH, Nah YW, Kim DS, Kim DJ, You YK, Yu HC. Liver transplantation for combined hepatocellular carcinoma and cholangiocarcinoma: A multicenter study. World J Gastrointest Surg 2023; 15:1340-1353. [PMID: 37555110 PMCID: PMC10405106 DOI: 10.4240/wjgs.v15.i7.1340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 01/03/2023] [Accepted: 04/19/2023] [Indexed: 07/21/2023] Open
Abstract
BACKGROUND Patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) are not traditionally considered eligible for liver transplantation (LT) due to poor outcomes. AIM To compare outcomes between living donor LT (LDLT) patients with hepatocellular carcinoma (HCC) and LT patients with cHCC-CC and to identify risk factors for tumor recurrence and death after LT in cHCC-CC patients. METHODS Data for pathologically diagnosed cHCC-CC patients (n = 111) who underwent LT from 2000 to 2018 were collected for a nine-center retrospective review. Patients (n = 141) who received LDLT for HCC at Samsung Medical Center from January 2013 to March 2017 were selected as the control group. Seventy patients in two groups, respectively, were selected by 1:1 matching. RESULTS Cumulative disease-free survival (DFS) and overall survival (OS) in the cHCC-CC group were significantly worse than in the HCC group both before and after matching. Extrahepatic recurrence incidence in the cHCC-CC group was higher than that in the HCC group (75.5% vs 33.3%, P < 0.001). Multivariate analysis demonstrated that the cHCC-CC group had significantly higher rates of tumor recurrence and death compared to the HCC group. In cHCC-CC subgroup analysis, frequency of locoregional therapies > 3, tumor size > 3 cm, and lymph node metastasis were predisposing factors for tumor recurrence in multivariate analysis. Only a maximum tumor size > 3 cm was a predisposing factor for death. CONCLUSION The poor prognosis of patients diagnosed with cHCC-CC after LT can be predicted based on the explanted liver. Frequent regular surveillance for cHCC-CC patients should be required for early detection of tumor recurrence.
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Affiliation(s)
- Jongman Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea
| | - Dong-Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul 03722, South Korea
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, South Korea
| | - Jeong-Moo Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul 03080, South Korea
| | - Je-Ho Ryu
- Department of Surgery, Pusan National University College of Medicine, Busan 50612, South Korea
| | - Yang-Won Nah
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, South Korea
| | - Dong-Sik Kim
- Department of Surgery, Korea University College of Medicine, Seoul 02841, South Korea
| | - Doo-Jin Kim
- Department of Surgery, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon 21565, South Korea
| | - Young-Kyoung You
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul 06591, South Korea
| | - Hee-Chul Yu
- Department of Surgery, Jeonbuk National University Medical School, Jeonju 54907, South Korea
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15
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Satake T, Shibuki T, Watanabe K, Sasaki M, Imaoka H, Mitsunaga S, Kojima M, Ikeda M. Case Report: Atezolizumab plus bevacizumab for combined hepatocellular-cholangiocarcinoma. Front Oncol 2023; 13:1234113. [PMID: 37546425 PMCID: PMC10401838 DOI: 10.3389/fonc.2023.1234113] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Accepted: 06/27/2023] [Indexed: 08/08/2023] Open
Abstract
Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a rare subtype of primary liver cancers. Therapeutic strategies for patients with cHCC-CCA are limited, and no standard systemic treatment has been established for unresectable cHCC-CCA. Here, we present six cases of cHCC-CCA treated with atezolizumab plus bevacizumab. We observed three partial responses and one stable disease as the best responses; two of these patients were still being treated with atezolizumab plus bevacizumab at the time of reporting (at least five months of treatment), whereas the remaining two patients were unable to continue treatment owing to adverse events. Atezolizumab plus bevacizumab may be an effective treatment for unresectable cHCC-CCA.
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Affiliation(s)
- Tomoyuki Satake
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Taro Shibuki
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Kazuo Watanabe
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Mitsuhito Sasaki
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Hiroshi Imaoka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Shuichi Mitsunaga
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Motohiro Kojima
- Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center Hospital East, Kashiwa, Japan
| | - Masafumi Ikeda
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
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Wu Y, Liu H, Chen Y, Zeng J, Huang Q, Zhang J, Zeng Y, Liu J. Prognostic significance of three-tiered pathological classification for microvascular invasion in patients with combined hepatocellular-cholangiocarcinoma following hepatic resection. Cancer Med 2023; 12:5233-5244. [PMID: 36354141 PMCID: PMC10028161 DOI: 10.1002/cam4.5328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 08/01/2022] [Accepted: 09/12/2022] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Previous studies have reported that the microvascular invasion three-tiered grading (MiVI-TTG) scheme is a better prognostic predictor than the two-tiered microvascular invasion (MiVI) grading scheme in hepatocellular carcinoma. This study aims to explore the prognostic significance of MiVI-TTG in patients undergoing liver resection for combined hepatocellular-cholangiocarcinoma (cHCC) and to explore the risk factors for MiVI in cHCC. METHODS This research included 208 patients graded as M0, M1, or M2 using the MiVI-TTG scheme. Predictive performance was assessed by Cox regression analysis, Kaplan-Meier curve with Log rank test, Harrell's c-index, and time-dependent areas under the receiver operating characteristic curve (tdAUC). The clinical utility of the two schemes was evaluated by decision cure analysis (DCA). The risk factors for MiVI were evaluated using logistic regression analysis. RESULTS Among 208 cHCC patients, the proportions of M0, M1 and M2 were 38.9%, 36.5%, and 24.5%, respectively. Patients with severe MiVI status had worse recurrence-free survival and overall survival (OS) based on Kaplan-Meier analysis. M1, M2, and MiVI-positive were independent risk factors for early recurrence, while M2 and MiVI-positive were associated with overall survival (OS). MiVI-TTG had a larger c-index, tdAUC, and net benefit rate than the two-tiered MiVI grading scheme for predicting recurrence free survival and OS. AFP≥400 ng/ml was the independent risk factor for MiVI, and satellite nodules were independent risk factors for M2. CONCLUSIONS MiVI-TTG has a greater prognostic value than the two-tiered MiVI grading scheme in patients undergoing hepatic resection for cHCC.
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Affiliation(s)
- Yijun Wu
- Department of Hepatobiliary SurgeryMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouPeople's Republic of China
| | - Hongzhi Liu
- Department of Hepatobiliary SurgeryMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouPeople's Republic of China
| | - Yifan Chen
- Shengli Clinical Medical College of Fujian Medical University
| | - Jianxing Zeng
- Department of Hepatobiliary SurgeryMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouPeople's Republic of China
| | - Qizhen Huang
- Department of Hepatobiliary SurgeryMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouPeople's Republic of China
| | - Jinyu Zhang
- Department of Hepatobiliary SurgeryMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouPeople's Republic of China
| | - Yongyi Zeng
- Department of Hepatobiliary SurgeryMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouPeople's Republic of China
| | - Jingfeng Liu
- Fujian Medical University Cancer Hospital & Fujian Cancer HospitalFuzhouFujianPeople's Republic of China
- The Big Data Institute of Southeast Hepatobiliary Health InformationMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouPeople's Republic of China
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Surgical Strategies for Combined Hepatocellular-Cholangiocarcinoma (cHCC-CC). Cancers (Basel) 2023; 15:cancers15030774. [PMID: 36765731 PMCID: PMC9913263 DOI: 10.3390/cancers15030774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/17/2023] [Accepted: 01/19/2023] [Indexed: 01/28/2023] Open
Abstract
Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a tumor entity presenting features of hepatocellular and cholangiocellular epithelial differentiation. Due to the likeness between cHCC-CC, HCC and CC, accurate pretherapeutical diagnosis is challenging and advanced stages are prevalent. Radical oncological surgery is the only curative therapeutical option in patients with cHCC-CC. To reach this goal a profound understanding of this rare liver tumor is crucial. Factors such as clinicopathological characteristics, growth patterns and biological behavior are of central importance. To explore onco-surgical strategies and aspects for complete resection of cHCC-CC and to answer important key questions, an extensive review of the literature was conducted to answer the following questions: What are the best surgical options? Is there a significance for nonanatomical resections? Is there a prognostic value of concomitant lymphadenectomy? What about multimodal concepts in local advanced cHCC-CC? The role of minimally invasive liver surgery (MILS) including the role of robotic liver surgery for cHCC-CC will be discussed. While liver transplantation (LT) is standard for patients with unresectable HCC, the role of LT in cHCC-CC patients is still controversial. How can patients with high risk for early tumor recurrence be identified to avoid aggressive surgical treatment without clinical benefit? The comprehensive understanding of this challenging liver tumor will help to improve future treatment options for these patients.
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18
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Mixed Hepatocellular Cholangiocarcinoma: A Comparison of Survival between Mixed Tumors, Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma from a Single Center. Cancers (Basel) 2023; 15:cancers15030639. [PMID: 36765596 PMCID: PMC9913586 DOI: 10.3390/cancers15030639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/16/2023] [Accepted: 01/17/2023] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most frequent primary liver malignancy, followed by intrahepatic cholangiocarcinoma (ICC). In addition, there is a mixed form for which only limited data are available. The aim of this study was to compare recurrence and survival of the mixed form within the cohorts of patients with HCC and ICC from a single center. METHODS Between January 2008 and December 2020, all patients who underwent surgical exploration for ICC, HCC, or mixed hepatocellular cholangiocarcinoma (mHC-CC) were included in this retrospective analysis. The data were analyzed, focusing on preoperative and operative details, histological outcome, and tumor recurrence, as well as overall and recurrence-free survival. RESULTS A total of 673 surgical explorations were performed, resulting in 202 resections for ICC, 344 for HCC (225 non-cirrhotic HCC, ncHCC; 119 cirrhotic HCC, cHCC), and 14 for mHC-CC. In addition, six patients underwent orthotopic liver transplant (OLT) in the belief of dealing with HCC. In 107 patients, tumors were irresectable (resection rate of 84%). Except for the cHCC group, major or even extended liver resections were required. Vascular or visceral extensions were performed regularly. Overall survival (OS) was highly variable, with a median OS of 17.6 months for ICC, 26 months for mHC-CC, 31.8 months for cHCC, and 37.2 months for ncHCC. Tumor recurrence was common, with a rate of 45% for mHC-CC, 48.9% for ncHCC, 60.4% for ICC, and 67.2% for cHCC. The median recurrence-free survival was 7.3 months for ICC, 14.4 months for cHCC, 16 months for mHC-CC, and 17 months for ncHCC. The patients who underwent OLT for mHC-CC showed a median OS of 57.5 and RFS of 56.5 months. CONCLUSIONS mHC-CC has a comparable course and outcome to ICC. The cholangiocarcinoma component seems to be the dominant one and, therefore, may be responsible for the prognosis. 'Accidental' liver transplant for mHC-CC within the Milan criteria offers a good long-term outcome. This might be an option in countries with no or minor organ shortage.
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Pathology of Combined Hepatocellular Carcinoma-Cholangiocarcinoma: An Update. Cancers (Basel) 2023; 15:cancers15020494. [PMID: 36672443 PMCID: PMC9856551 DOI: 10.3390/cancers15020494] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 01/08/2023] [Accepted: 01/11/2023] [Indexed: 01/15/2023] Open
Abstract
Combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer that is composed of both hepatocellular and cholangiocellular differentiated cells. It is slightly more common in men and among Asian and Pacific islanders. Overall, risk factors are similar to classic risk factors of hepatocellular carcinoma (HCC). The classification has significantly evolved over time. The last WHO classification (2019) mainly emphasized diagnosis on morphological basis with routine stainings, discarded previously recognized classifications with carcinomas with stem cell features, introduced intermediate cell carcinoma as a specific subtype and considered cholangiolocarcinoma as a subtype of cholangiocellular carcinoma. Immunohistochemical markers may be applied for further specification but have limited value for diagnosis. Recent discoveries in molecular pathway regulation may pioneer new therapeutic approaches for this poor prognostic and challenging diagnosis.
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Eschrich J, Kobus Z, Geisel D, Halskov S, Roßner F, Roderburg C, Mohr R, Tacke F. The Diagnostic Approach towards Combined Hepatocellular-Cholangiocarcinoma-State of the Art and Future Perspectives. Cancers (Basel) 2023; 15:cancers15010301. [PMID: 36612297 PMCID: PMC9818385 DOI: 10.3390/cancers15010301] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 12/17/2022] [Accepted: 12/27/2022] [Indexed: 01/03/2023] Open
Abstract
Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer which displays clinicopathologic features of both hepatocellular (HCC) and cholangiocellular carcinoma (CCA). The similarity to HCC and CCA makes the diagnostic workup particularly challenging. Alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9) are blood tumour markers related with HCC and CCA, respectively. They can be used as diagnostic markers in cHCC-CCA as well, albeit with low sensitivity. The imaging features of cHCC-CCA overlap with those of HCC and CCA, dependent on the predominant histopathological component. Using the Liver Imaging and Reporting Data System (LI-RADS), as many as half of cHCC-CCAs may be falsely categorised as HCC. This is especially relevant since the diagnosis of HCC may be made without histopathological confirmation in certain cases. Thus, in instances of diagnostic uncertainty (e.g., simultaneous radiological HCC and CCA features, elevation of CA 19-9 and AFP, HCC imaging features and elevated CA 19-9, and vice versa) multiple image-guided core needle biopsies should be performed and analysed by an experienced pathologist. Recent advances in the molecular characterisation of cHCC-CCA, innovative diagnostic approaches (e.g., liquid biopsies) and methods to analyse multiple data points (e.g., clinical, radiological, laboratory, molecular, histopathological features) in an all-encompassing way (e.g., by using artificial intelligence) might help to address some of the existing diagnostic challenges.
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Affiliation(s)
- Johannes Eschrich
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum and Campus Charité Mitte, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Zuzanna Kobus
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum and Campus Charité Mitte, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Dominik Geisel
- Department for Radiology, Campus Virchow Klinikum, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Sebastian Halskov
- Department for Radiology, Campus Virchow Klinikum, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Florian Roßner
- Department of Pathology, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany
| | - Christoph Roderburg
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty of Heinrich Heine University Düsseldorf, University Hospital Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany
| | - Raphael Mohr
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum and Campus Charité Mitte, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum and Campus Charité Mitte, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
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21
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Sakano Y, Noda T, Kobayashi S, Kitagawa A, Iwagami Y, Yamada D, Tomimaru Y, Akita H, Gotoh K, Asaoka T, Tanemura M, Umeshita K, Mimori K, Doki Y, Eguchi H. Clinical Significance of Acylphosphatase 1 Expression in Combined HCC-iCCA, HCC, and iCCA. Dig Dis Sci 2022; 67:3817-3830. [PMID: 34626299 DOI: 10.1007/s10620-021-07266-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Accepted: 09/27/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND Combined hepatocellular and cholangiocarcinoma is a rare primary liver cancer with histological features of both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Little is known about the prognostic features and molecular mechanism of cHCC-iCCA. Acylphosphatase 1 is a cytosolic enzyme that produces acetic acid from acetyl phosphate and plays an important role in cancer progression. AIMS We evaluated the clinical significance of ACYP1 expression in cHCC-iCCA, HCC, and iCCA. METHODS ACYP1 immunohistochemistry was performed in 39 cases diagnosed with cHCC-iCCA. The prognosis was evaluated in three different cohorts (cHCC-iCCA, HCC, and iCCA). The relationships between ACYP1 expression and cell viability, migration, invasiveness, and apoptosis were examined using siRNA methods in vitro. In vivo subcutaneous tumor volumes and cell apoptosis were evaluated after downregulation of ACYP1 expression. RESULTS Almost half of the patients with cHCC-iCCA were diagnosed with high ACYP1 expression. In all three cohorts, the cases with high ACYP1 expression had significantly lower overall survival, and high ACYP1 expression was identified as an independent prognostic factor. Downregulation of ACYP1 reduced the proliferative capacity, migration, and invasiveness of both HCC and iCCA cells. Moreover, knockdown of ACYP1 increased the ratio of apoptotic cells and decreased the expression of anti-apoptosis proteins. In vivo tumor growth was significantly inhibited by the transfection of ACYP1 siRNA, and the number of apoptotic cells increased. CONCLUSION High ACYP1 expression could influence the prognosis of cHCC-iCCA, HCC, and iCCA patients. In vitro ACYP1 expression influences the tumor growth and cell viability in both HCC and iCCA by regulating anti-apoptosis proteins.
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Affiliation(s)
- Yoshihiro Sakano
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Takehiro Noda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
| | - Akihiro Kitagawa
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yoshifumi Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Daisaku Yamada
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yoshito Tomimaru
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hirofumi Akita
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Kunihito Gotoh
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Tadafumi Asaoka
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan
- Department of Surgery, Osaka Police Hospital, Osaka, Japan
| | - Masahiro Tanemura
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan
- Department of Surgery, Rinku General Medical Center, Osaka, Japan
| | - Koji Umeshita
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Koshi Mimori
- Department of Surgery, Kyushu University Beppu Hospital, Oita, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan
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22
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Lee SJ, Kang SH, Choi Y, Lee B, Hong S, Cho JY, Yi N, Lee K, Suh K, Han H. Long-term outcomes of laparoscopic versus open liver resection for intrahepatic combined hepatocellular-cholangiocarcinoma with propensity score matching. Ann Gastroenterol Surg 2022; 6:562-568. [PMID: 35847442 PMCID: PMC9271021 DOI: 10.1002/ags3.12555] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 01/04/2022] [Accepted: 02/01/2022] [Indexed: 11/23/2022] Open
Abstract
Background Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary hepatic neoplasm. Currently, there are no well-structured studies that analyze the feasibility of laparoscopic liver resection in cHCC-CCA alone. This retrospective cohort study aimed to compare the long-term survival of laparoscopic liver resection with open liver resection in cHCC-CCA. Methods Patients with a postoperative pathologic report of cHCC-CCA who underwent liver resection from August 2004 to December 2017 were included in this study. Kaplan-Meier survival analysis was performed to analyze the 3-y disease-free survival and 3-y overall survival. Propensity score matching was done to reduce the influence of confounding variables. Results A total of 145 patients were pathologically confirmed to have cHCC-CCA, of which 10 patients were excluded due to having received palliative surgery. Of the remaining 135 patients, 43 underwent laparoscopic and 92 underwent open liver resection; propensity score matching yielded 30 patients for each group. The 3-y overall survival was 38 (88.4%) in the laparoscopic group and 84 (91.3%) in the open group before propensity score matching (P = .678), and 25 (83.3%) and 28 (93.3%), respectively, after matching (P = .257). The 3-y disease-free survival was 24 (55.8%) in the laparoscopic group and 32 (34.8%) in the open group before matching (P = .040), and 17 (56.7%) and 16 (53.3%), respectively, after matching (P = .958). The hospital stay was shorter in the laparoscopic group before and after matching, while other operative outcomes were similar in both groups. Conclusion Laparoscopic liver resection for cHCC-CCA is technically feasible and safe, having a shorter hospital stay without compromising oncological outcomes.
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Affiliation(s)
- Seung Jae Lee
- Department of SurgerySeoul National University College of MedicineSeoul National University HospitalSeoulKorea
| | - So Hyun Kang
- Department of SurgerySeoul National University College of MedicineSeoul National University Bundang HospitalSeongnamKorea
| | - YoungRok Choi
- Department of SurgerySeoul National University College of MedicineSeoul National University HospitalSeoulKorea
- Department of SurgerySeoul National University College of MedicineSeoul National University Bundang HospitalSeongnamKorea
| | - Boram Lee
- Department of SurgerySeoul National University College of MedicineSeoul National University Bundang HospitalSeongnamKorea
| | - Suk Kyun Hong
- Department of SurgerySeoul National University College of MedicineSeoul National University HospitalSeoulKorea
| | - Jai Young Cho
- Department of SurgerySeoul National University College of MedicineSeoul National University Bundang HospitalSeongnamKorea
| | - Nam‐Joon Yi
- Department of SurgerySeoul National University College of MedicineSeoul National University HospitalSeoulKorea
| | - Kwang‐Woong Lee
- Department of SurgerySeoul National University College of MedicineSeoul National University HospitalSeoulKorea
| | - Kyung‐Suk Suh
- Department of SurgerySeoul National University College of MedicineSeoul National University HospitalSeoulKorea
| | - Ho‐Seong Han
- Department of SurgerySeoul National University College of MedicineSeoul National University Bundang HospitalSeongnamKorea
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23
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Zhou YW, Li QF, Chen YY, Wang K, Pu D, Chen XR, Li CH, Jiang L, Wang Y, Li Q, Yang Y, Gou HF, Bi F, Liu JY, Chen Y, Qiu M. Clinicopathologic features, treatment, survival, and prognostic factors of combined hepatocellular and cholangiocarcinoma: A nomogram development based on SEER database and validation in multicenter study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:1559-1566. [PMID: 35115213 DOI: 10.1016/j.ejso.2022.01.023] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 10/07/2021] [Accepted: 01/23/2022] [Indexed: 02/05/2023]
Abstract
PURPOSE The aim of the study was to comprehensively understand the combined hepatocellular and cholangiocarcinoma (CHC) and develop a nomogram for prognostic prediction of CHC. METHODS Data were collected from the Surveillance, Epidemiology and End Results (SEER) database (year 2004-2014). Propensity-score matching (PSM) was used to match the demographic characteristic of the CHC versus hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). A nomogram model was established to predict the prognosis in terms of cancer specific survival (CSS). The established nomogram was externally validated by a multicenter cohort. RESULTS A total of 71,756 patients enrolled in our study including 62,877 HCC patients, 566 CHC patients, and 8303 ICC patients. The CHC, HCC, and ICC are not exactly similar in clinical characteristic. After PSM, the CSS of CHC was better than HCC but comparable to ICC. Tumor size, M stage, surgery, chemotherapy, and surgery were independently prognostic factors of CHC and were included in the establishment of novel nomogram. The c-index of the novel nomogram in SEER training set and multicenter validation was 0.779 and 0.780, respectively, which indicated that the model was with better discrimination power. In addition, decision curve analyses proved the favorable potential clinical effect of the predictive model. Lastly, a risk classification based on nomogram also verified the reliability of the model. CONCLUSION CHC had better survival than HCC but was comparable to ICC. The nomogram was established based on tumor size, M stage, chemotherapy, surgery, and radiotherapy and well validated by external multicenter cohort.
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Affiliation(s)
- Yu-Wen Zhou
- Department of Biotherapy, Cancer Center, West China Hospital of Sichuan University, Chengdu, China; Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, China
| | - Qing-Fang Li
- Department of Biotherapy, Cancer Center, West China Hospital of Sichuan University, Chengdu, China; Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, China
| | - Yue-Yun Chen
- Department of Biotherapy, Cancer Center, West China Hospital of Sichuan University, Chengdu, China; Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, China
| | - Kai Wang
- Institute for Emergency Medicine and Disaster Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, China
| | - Dan Pu
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xiao-Rong Chen
- Department of Abdominal Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China
| | - Chun-Hong Li
- Department of Oncology, Suining Central Hospital, Suining, China
| | - Li Jiang
- Department of Abdominal Oncology, Sichuan Cancer Hospital, Chengdu, China
| | - Yan Wang
- Department of Oncology, The First People's Hospital of Long Quan Yi District, Chengdu, China
| | - Qiu Li
- Department of Abdominal Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China
| | - Yu Yang
- Department of Abdominal Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China
| | - Hong-Feng Gou
- Department of Abdominal Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China
| | - Feng Bi
- Department of Abdominal Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China
| | - Ji-Yan Liu
- Department of Biotherapy, Cancer Center, West China Hospital of Sichuan University, Chengdu, China; Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, China.
| | - Ye Chen
- Department of Abdominal Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China.
| | - Meng Qiu
- Department of Abdominal Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China.
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Wen R, Lin P, Wu Y, Yin H, Huang W, Guo D, Peng Y, Liu D, He Y, Yang H. Diagnostic value of CEUS LI-RADS and serum tumor markers for combined hepatocellular-cholangiocarcinoma. Eur J Radiol 2022; 154:110415. [PMID: 35738166 DOI: 10.1016/j.ejrad.2022.110415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Revised: 05/10/2022] [Accepted: 06/15/2022] [Indexed: 11/03/2022]
Abstract
PURPOSE To analyze the contrast-enhanced ultrasound (CEUS) manifestations of combined hepatocellular-cholangiocarcinoma (CHC) and to investigate the diagnostic value of the 2017 version of the CEUS Liver Imaging Reporting and Data System (LI-RADS) and serum tumor markers in CHC. METHODS A total of 66 pathologically confirmed CHC nodules were retrospectively analyzed. We summarized the CEUS manifestations of CHC and analyzed the relationship between serum tumor markers and the enhancement pattern of CHC. We also classified CHC according to CEUS LI-RADS criteria. The Kappa test was used to assess the interreader agreement of CEUS LI-RADS between radiologists. RESULT According to the results, 52 of 62 (83.9%) patients had elevated alpha-fetoprotein (AFP), 19 of 61 (31.1%) had elevated carbohydrate antigen 199 (CA 199), and 13 of 61 (21.3%) had both elevated AFP and CA 199. Of the 66 CHC nodules, 64 (97.0%) were identified as malignant lesions by CEUS, 13 (19.7%) showed a hepatocellular carcinoma-like enhancement pattern, and 21 (31.8%) showed a cholangiocarcinoma-like enhancement pattern. For the CEUS LI-RADS categories, 39 of 53 (73.6%) CHC nodules were classified as LR-M, 12 (22.6%) were classified as LR-5, and 2 (3.8%) were classified as LR-4. The interreader agreement for the LI-RADS categories was 0.60. CONCLUSIONS Although CHC lacks specific CEUS features, CEUS LI-RADS and serum tumor markers can be useful tools for reducing the misdiagnosis of CHC. In addition, due to the relative complexity of the CEUS features involved in CHC, it is necessary for beginning radiologists to learn more about CEUS features.
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Affiliation(s)
- Rong Wen
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Peng Lin
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Yuquan Wu
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Haihui Yin
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Weiche Huang
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Danxia Guo
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Yuye Peng
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Dun Liu
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Yun He
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Hong Yang
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.
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Chen Y, Lu Q, Zhang W, Cao J, Dong Y, Wang W. Preoperative Differentiation of Combined Hepatocellular-Cholangiocarcinoma From Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: A Nomogram Based on Ultrasonographic Features and Clinical Indicators. Front Oncol 2022; 12:757774. [PMID: 35242699 PMCID: PMC8885729 DOI: 10.3389/fonc.2022.757774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 01/24/2022] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE To establish a predictive nomogram to distinguish combined hepatocellular-cholangiocarcinoma (CHC) from hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) based on preoperative clinical and ultrasound findings. METHODS A total of 261 patients with pathologically confirmed primary liver cancers (PLCs) were enrolled in this retrospective study, comprising 87 CHCs, 87 HCCs, and 87 ICCs matched by propensity score matching. Patients were randomly assigned to a training cohort and a validation one at the ratio of 7:3. A nomogram integrating ultrasound imaging characteristics and clinical features was established based on the independent risk factors selected by least absolute shrinkage and selection operator (LASSO) regression. The performance of the nomogram was evaluated in the training and validation cohorts in terms of discrimination, calibration, and clinical usefulness. RESULTS The nomogram, consisting of ultrasound imaging features (shape and margin on B-mode ultrasound, enhanced pattern on contrast-enhanced ultrasound) and clinical information [elevated alpha fetoprotein (AFP) level and serum protein electrophoresis (SPE) α1 level], showed promising performance in differentiating CHC from HCC and ICC, with the concordance index (C-index) of 0.8275 and 0.8530 in the training cohort and the validation cohort, respectively. Hosmer-Lemeshow test and the calibration curves suggested good consistency between predictions and observations. High clinical practicability was confirmed by the decision curve analysis. CONCLUSIONS The nomogram based on clinical and ultrasound imaging characteristics showed good performance in the discrimination of CHC from other subtypes of PLC and would be valuable in clinical decision-making.
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Affiliation(s)
- Yanling Chen
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qing Lu
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Weibin Zhang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jiaying Cao
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yi Dong
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wenping Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China.,Shanghai Institute of Medical Imaging, Shanghai, China
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Wu Y, Liu H, Zeng J, Chen Y, Fang G, Zhang J, Zhou W, Zeng Y, Liu J. Development and validation of nomogram to predict very early recurrence of combined hepatocellular-cholangiocarcinoma after hepatic resection: a multi-institutional study. World J Surg Oncol 2022; 20:60. [PMID: 35227269 PMCID: PMC8883704 DOI: 10.1186/s12957-022-02536-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 02/18/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Combined hepatocellular cholangiocarcinoma (cHCC) has a high incidence of early recurrence. The objective of this study is to construct a model predicting very early recurrence (VER) (i.e., recurrence within 6 months after surgery) of cHCC. METHODS One hundred thirty-one consecutive patients from Eastern Hepatobiliary Surgery Hospital served as a development cohort to construct a nomogram predicting VER by using multi-variable logistic regression analysis. The model was internally and externally validated in a validation cohort of 90 patients from Mengchao Hepatobiliary Hospital using the C concordance statistic, calibration analysis, and decision curve analysis (DCA). RESULTS The VER nomogram contains microvascular invasion (MiVI), macrovascular invasion (MaVI), and CA19-9 > 25 mAU/mL. The model shows good discrimination with C-indexes of 0.77 (95% CI: 0.69-0.85) and 0.76 (95% CI: 0.66-0.86) in the development cohort and validation cohort respectively. Decision curve analysis demonstrated that the model is clinically useful and the calibration of our model was favorable. Our model stratified patients into two different risk groups, which exhibited significantly different VER. CONCLUSIONS Our model demonstrated favorable performance in predicting VER in cHCC patients.
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Affiliation(s)
- Yijun Wu
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People's Republic of China
| | - Hongzhi Liu
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People's Republic of China
| | - Jianxing Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People's Republic of China
| | - Yifan Chen
- Shengli Clinical Medical College of Fujian Medical University, Fuzhoum, People's Republic of China
| | - Guoxu Fang
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People's Republic of China
| | - Jinyu Zhang
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People's Republic of China
| | - Weiping Zhou
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, People's Republic of China
| | - Yongyi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People's Republic of China.
| | - Jingfeng Liu
- Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, No. 420, Fuma Road, Fuzhou, 350014, Fujian, People's Republic of China.
- The Big Data Institute of Southeast Hepatobiliary Health Information, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People's Republic of China.
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27
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Mukund A, V Srinivasan S, Rana S, Vijayaraghavan R, Patidar Y, Arora V, Jindal A, Choudhury A, Shasthry SM, Sarin SK. Response evaluation of locoregional therapies in combined hepatocellular-cholangiocarcinoma and intrahepatic cholangiocarcinoma versus hepatocellular carcinoma: a propensity score matched study. Clin Radiol 2022; 77:121-129. [PMID: 34789395 DOI: 10.1016/j.crad.2021.10.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 10/14/2021] [Indexed: 11/16/2022]
Abstract
AIM To evaluate the response of locoregional therapy (LRT) on combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (IHC) and compare their outcomes with propensity matched hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS From January 2011 to July 2020, 13 patients with cHCC-CC (11 men, two women, median age 56 years) and 15 IHC patients (10 men, five women, median age 60 years) were compared with 101 HCC patients (79 men, 22 women, median age 60 years) after LRT. All tumours were proven histologically. Among the 13 cHCC-CC patients, 11 received transarterial chemoembolisation (TACE), one received microwave ablation (MWA) and one received TACE with radiofrequency ablation (RFA). Of 15 IHC patients, eight received TACE, five received RFA, and one received MWA, and one received TACE with RFA. Propensity score matching (PSM) was done with conditional logistic regression adjusted for age, type of LRT, tumour specific features and Child-Pugh score. RESULTS After LRT, on univariate analysis an objective response was seen in 30% of cHCC-CC and 53% of IHC patients. PSM analysis demonstrated shorter progression-free survival (PFS; cHCC-CC versus HCC: 1.5 versus 7.5 months; IHC versus HCC: 6 versus 14 months, p<0.05), overall survival (OS; cHCC-CC versus HCC: 12 versus 28 months; IHC versus HCC: 18 versus 34 months, p<0.005), and poor objective response (cHCC-CC versus HCC: 25% versus 91%; IHC versus HCC: 58% versus 88%, p<0.05) in cHCC-CC and IHC patients versus HCC patients. Hypovascular tumour, macrovascular invasion, and infiltrative appearance were independent prognostic factors for OS in IHC patients. CONCLUSION cHCC-CC and IHC are aggressive tumours with a poor objective response, greater distant progression of the disease and shorter PFS and OS post LRT as compared to HCC.
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Affiliation(s)
- A Mukund
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, New Delhi, India.
| | - S V Srinivasan
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - S Rana
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - R Vijayaraghavan
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Y Patidar
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - V Arora
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - A Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - A Choudhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - S M Shasthry
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - S K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Kovač JD, Janković A, Đikić-Rom A, Grubor N, Antić A, Dugalić V. Imaging Spectrum of Intrahepatic Mass-Forming Cholangiocarcinoma and Its Mimickers: How to Differentiate Them Using MRI. Curr Oncol 2022; 29:698-723. [PMID: 35200560 PMCID: PMC8870737 DOI: 10.3390/curroncol29020061] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 01/23/2022] [Accepted: 01/29/2022] [Indexed: 12/14/2022] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy, with mass-forming growth pattern being the most common. The typical imaging appearance of mass-forming ICC (mICC) consists of irregular ring enhancement in the arterial phase followed by the progressive central enhancement on portal venous and delayed phases. However, atypical imaging presentation in the form of hypervascular mICC might also be seen, which can be attributed to distinct pathological characteristics. Ancillary imaging features such as lobular shape, capsular retraction, segmental biliary dilatation, and vascular encasement favor the diagnosis of mICC. Nevertheless, these radiological findings may also be present in certain benign conditions such as focal confluent fibrosis, sclerosing hemangioma, organizing hepatic abscess, or the pseudosolid form of hydatid disease. In addition, a few malignant lesions including primary liver lymphoma, hemangioendothelioma, solitary hypovascular liver metastases, and atypical forms of hepatocellular carcinoma (HCC), such as scirrhous HCC, infiltrative HCC, and poorly differentiated HCC, may also pose a diagnostic dilemma by simulating mICC in imaging studies. Diffusion-weighted imaging and the use of hepatobiliary contrast agents might be helpful for differential diagnosis in certain cases. The aim of this manuscript is to provide a comprehensive overview of mICC imaging features and to describe useful tips for differential diagnosis with its potential mimickers.
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Affiliation(s)
- Jelena Djokic Kovač
- Center for Radiology and Magnetic Resonance Imaging, University Clinical Centre of Serbia, Pasterova No. 2, 11000 Belgrade, Serbia;
- Faculty of Medicine, University of Belgrade, Dr Subotica No. 8, 11000 Belgrade, Serbia; (N.G.); (A.A.); (V.D.)
- Correspondence: ; Tel.: +381-65-8270-290
| | - Aleksandra Janković
- Center for Radiology and Magnetic Resonance Imaging, University Clinical Centre of Serbia, Pasterova No. 2, 11000 Belgrade, Serbia;
| | - Aleksandra Đikić-Rom
- Department of Pathology, University Clinical Centre of Serbia, Pasterova No.2, 11000 Belgrade, Serbia;
| | - Nikica Grubor
- Faculty of Medicine, University of Belgrade, Dr Subotica No. 8, 11000 Belgrade, Serbia; (N.G.); (A.A.); (V.D.)
- Clinic for Digestive Surgery, University Clinical Centre of Serbia, Koste Todorovica Street, No. 6, 11000 Belgrade, Serbia
| | - Andrija Antić
- Faculty of Medicine, University of Belgrade, Dr Subotica No. 8, 11000 Belgrade, Serbia; (N.G.); (A.A.); (V.D.)
- Clinic for Digestive Surgery, University Clinical Centre of Serbia, Koste Todorovica Street, No. 6, 11000 Belgrade, Serbia
| | - Vladimir Dugalić
- Faculty of Medicine, University of Belgrade, Dr Subotica No. 8, 11000 Belgrade, Serbia; (N.G.); (A.A.); (V.D.)
- Clinic for Digestive Surgery, University Clinical Centre of Serbia, Koste Todorovica Street, No. 6, 11000 Belgrade, Serbia
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Hou GM, Jiang C, Du JP, Yuan KF. Sarcopenia predicts an adverse prognosis in patients with combined hepatocellular carcinoma and cholangiocarcinoma after surgery. Cancer Med 2021; 11:317-331. [PMID: 34866356 PMCID: PMC8729053 DOI: 10.1002/cam4.4448] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 11/05/2021] [Accepted: 11/08/2021] [Indexed: 02/05/2023] Open
Abstract
Background The prognostic value of sarcopenia in combined hepatocellular carcinoma and cholangiocarcinoma (cHCC‐CC) patients after surgery has not been evaluated, while the efficacy of the available tumor stage for cHCC‐CC remains controversial. Methods All consecutive cHCC‐CC patients after surgery were retrieved. The patients were stratified by the sex‐specific medians of the psoas muscle index into groups with or without sarcopenia. Prognosis was analyzed using the Kaplan–Meier (K–M) method, and the K–M curves were adjusted by inverse probability weighting (IPW). A nomogram based on Cox regression analysis was established and further compared with primary liver cancer (PLC) stages by internal validation based on bootstrap resampling and k‐fold cross‐validation. Results A total of 153 patients were stratified into sarcopenia and non‐sarcopenia groups. The sarcopenia group revealed statistically worse overall survival (OS) and disease‐free survival (DFS) using the K–M method and K–M curves adjusted by IPW. Multivariate Cox regression analyses suggested sarcopenia as an independent risk factor for OS (HR = 1.55; p = 0.040) and DFS (HR = 1.55; p = 0.019). Subgroup analysis based on baseline variables showed sarcopenia as a stable risk factor for the prognosis. Our nomogram outperformed PLC stages in prognostic prediction, as evidenced by the best c‐index, area under the curve, and positive improvement of the net reclassification index and integrated discrimination improvement. A fivefold cross‐validation revealed consistent results. Decision curve analysis revealed higher net benefits of the nomogram than PLC stages. Conclusions Sarcopenia is an independent and stable risk factor for the prognosis of cHCC‐CC patients after surgery. Our nomogram might aid high‐risk patient identification and clinical decisions.
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Affiliation(s)
- Gui-Min Hou
- Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Chuang Jiang
- Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Jin-Peng Du
- Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Ke-Fei Yuan
- Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
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Qu MM, Zhu YH, Li YX, Li ZF, Li JK, Xu YS, Shrestha M, Lei JQ. Synchronous double primary hepatocellular carcinoma and intrahepatic cholangiocarcinoma: A case report and review of the literature. Medicine (Baltimore) 2021; 100:e27349. [PMID: 34797273 PMCID: PMC8601323 DOI: 10.1097/md.0000000000027349] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 09/09/2021] [Indexed: 01/05/2023] Open
Abstract
RATIONALE Presence of synchronous double hepatocelluar carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) (sdpHCC-ICC) located separately within a single liver is extremely rare. The purpose of this study is to investigate the clinical, imaging, pathological characteristics, and prognosis of patients with sdpHCC-ICC, in order to enhance our understanding of the disease and improve diagnostic and therapeutic effect. PATIENT CONCERNS A 49-year-old, female with the diagnosis of hepatitis B virus with obvious liver cirrhosis, was admitted to our hospital. On admission, the levels of α-fetoprotein and carbohydrate antigen 19-9 were found to be elevated. Abdominal ultrasonography and enhanced computed tomography revealed 2 solid masses located in segments (S) 4 and 6 of the liver, with malignant behaviors. DIAGNOSES In the light of above investigations, preoperative diagnosis of multiple primary hepatocellular carcinomas was made. INTERVENTION Hepatic resection of both segments was done. The resected specimens revealed the presence of well-defined tumors in segments 4 and 6 measuring 5.0 cm and 2.5 cm respectively. OUTCOMES Histopathological examination confirmed the tumor of the 4th segment to be moderately and poorly differentiated ICC, and the tumor of the 6th segment to be poorly differentiated HCC. Immunohistochemically, the ICC in S4 was positive for CK19 and negative for Heppar-1, whereas the HCC in S6 was positive for Heppar-1 and negative for CK19. Unfortunately, metastasis to multiple organs and lymph nodes were observed 3 months later. The patient died of liver failure 16 months after surgery. LESSONS The clinical characteristics of sdpHCC-ICC are usually atypical and nonspecific making its preoperative diagnosis quite difficult. Hepatitis B virus and hepatitis C virus infection were both the independent risk factor for the development of sdpHCC-ICC. In patients with chronic liver disease, careful observation with imaging is of utmost necessity. Tumor markers may also play a valuable role in the diagnosis. The definite diagnosis depends on pathological examination. Hepatic resection is considered the most effective mode of treatment. The prognosis of synchronous occurrence of double hepatic cancers is worse than either HCC or ICC, and the origin of the disease needs further study.
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Affiliation(s)
- Meng-Meng Qu
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
- Department of Radiology, The First Hospital of Lanzhou University, Lanzhou, China
| | - Yuan-Hui Zhu
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
- Department of Radiology, The First Hospital of Lanzhou University, Lanzhou, China
| | - Yi-Xiang Li
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
- Department of Radiology, The First Hospital of Lanzhou University, Lanzhou, China
| | - Zhi-Fan Li
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
- Department of Radiology, The First Hospital of Lanzhou University, Lanzhou, China
| | - Jin-Kui Li
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
- Department of Radiology, The First Hospital of Lanzhou University, Lanzhou, China
| | - Yong-Sheng Xu
- Department of Radiology, The First Hospital of Lanzhou University, Lanzhou, China
| | | | - Jun-Qiang Lei
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
- Department of Radiology, The First Hospital of Lanzhou University, Lanzhou, China
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Nguyen CT, Caruso S, Maille P, Beaufrère A, Augustin J, Favre L, Pujals A, Boulagnon-Rombi C, Rhaiem R, Amaddeo G, di Tommaso L, Luciani A, Regnault H, Brustia R, Scatton O, Charlotte F, Brochériou I, Sommacale D, Soussan P, Leroy V, Laurent A, Le VK, Ta VT, Trinh HS, Tran TL, Gentien D, Rapinat A, Nault JC, Allaire M, Mulé S, Zucman-Rossi J, Pawlotsky JM, Tournigand C, Lafdil F, Paradis V, Calderaro J. Immune profiling of combined hepatocellular-cholangiocarcinoma reveals distinct subtypes and activation of gene signatures predictive of response to immunotherapy. Clin Cancer Res 2021; 28:540-551. [PMID: 34785581 DOI: 10.1158/1078-0432.ccr-21-1219] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 06/18/2021] [Accepted: 11/09/2021] [Indexed: 11/16/2022]
Abstract
Purpose: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare malignancy associated with an overall poor prognosis. We aimed to investigate the immune profile of cHCC-CCA and determine its impact on disease outcome. Experimental Design: We performed a multicenter study of 96 patients with cHCC-CCA. Gene expression profile was analyzed using nCounter PanCancer IO 360 Panel. Densities of main immune cells subsets were quantified from digital slides of immunohistochemical stainings. Genetic alterations were investigated using targeted next generation sequencing. Results: Two main immune subtypes of cHCC-CCA were identified by clustering analysis: an "Immune High" (IH) subtype (57% of the cases) and an "Immune Low" (IL) subtype (43% of the cases). Tumors classified as IH showed overexpression of genes related to immune cells recruitment, adaptive and innate immunity, antigen presentation, cytotoxicity, immune suppression, and inflammation (p<0.0001). IH cHCC-CCAs also displayed activation of gene signatures recently shown to be associated with response to immunotherapy in patients with HCC. Immunostainings confirmed that IH tumors were also characterized by higher densities of immune cells. Immune subtypes were not associated with any genetic alterations. Finally, multivariate analysis showed that the IH subtype was an independent predictor of improved overall survival. Conclusions: We have identified a subgroup of cHCC-CCA that displays features of an ongoing intra-tumor immune response, along with an activation of gene signatures predictive of response to immunotherapy in HCC. This tumor subclass is associated with an improved clinical outcome. These findings suggest that a subset of patients with cHCC-CCA may benefit from immunomodulating therapeutic approaches.
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Affiliation(s)
- Cong Trung Nguyen
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
| | - Stefano Caruso
- INSERM UMR-1162, Génomique Fonctionnelle des Tumeurs Solides, Paris, France
| | - Pascale Maille
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Département de Pathologie, Créteil, France
| | - Aurélie Beaufrère
- Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, Service d'Anatomo-Pathologie, Clichy, France
| | - Jérémy Augustin
- Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service d'Anatomie et de Cytologie Pathologiques, Sorbonne Université, Paris, France
| | - Loetitia Favre
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Département de Pathologie, Créteil, France
| | - Anaïs Pujals
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Département de Pathologie, Créteil, France
| | - Camille Boulagnon-Rombi
- Centre Hospitalier Universitaire de Reims, Service d'Anatomie et de Cytologie Pathologiques, Reims, France
| | - Rami Rhaiem
- Hôpital Robert Debré, Service de Chirurgie Digestive et Hépatobiliaire, Reims, France
| | - Giuliana Amaddeo
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service d'Hépatologie, Créteil, France
| | - Luca di Tommaso
- Department of Pathology, Humanitas University, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy
| | - Alain Luciani
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service d'Imagerie Médicale, Créteil, France
| | - Hélène Regnault
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service d'Hépatologie, Créteil, France
| | - Raffaele Brustia
- Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service de Chirurgie Digestive, Hépato-Bilio-Pancréatique et Transplantation Hépatique, Paris, France
| | - Olivier Scatton
- Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service de Chirurgie Digestive, Hépato-Bilio-Pancréatique et Transplantation Hépatique, Paris, France
| | - Frédéric Charlotte
- Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service d'Anatomie et de Cytologie Pathologiques, Sorbonne Université, Paris, France
| | - Isabelle Brochériou
- Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service d'Anatomie et de Cytologie Pathologiques, Sorbonne Université, Paris, France
| | - Daniele Sommacale
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service de Chirurgie Digestive et Hépato-bilio-pancréatique, Créteil, France
| | - Patrick Soussan
- Centre National de la Recherche Scientifique (CNRS, ERL8255), Institut National de la Santé et de la Recherche Médicale (Inserm, UMR1135), Sorbonne Universités, Paris, France
| | - Vincent Leroy
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service d'Hépatologie, Créteil, France
| | - Alexis Laurent
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service de Chirurgie Digestive et Hépato-bilio-pancréatique, Créteil, France
| | - Van Ky Le
- Department of Pathology, National Cancer Hospital, Hanoi, Vietnam
| | - Van To Ta
- Department of Pathology, National Cancer Hospital, Hanoi, Vietnam
| | - Hong Son Trinh
- Department of Surgical Oncology, Vietduc Hospital, Hanoi, Vietnam
| | - Thi Lan Tran
- Department of Pathology, Hanoi Medical University, Hanoi, Vietnam
| | - David Gentien
- Institut Curie, PSL Research University, Translational Research Department, Genomics platform, Paris, France
| | - Audrey Rapinat
- Institut Curie, PSL Research University, Translational Research Department, Genomics platform, Paris, France
| | - Jean Charles Nault
- INSERM UMR-1162, Génomique Fonctionnelle des Tumeurs Solides, Paris, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Jean Verdier, Service d'Hépatologie, Bondy, France
| | - Manon Allaire
- Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service d'Hépatologie, Paris, France
| | - Sebastien Mulé
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service d'Imagerie Médicale, Créteil, France
| | - Jessica Zucman-Rossi
- INSERM UMR-1162, Génomique Fonctionnelle des Tumeurs Solides, Paris, France
- Assistance Publique-Hôpitaux de Paris, Service d'Oncologie Médicale, Hôpital Européen Georges Pompidou, Paris, France
- Université Paris Descartes, Université Paris Diderot, Université Paris 13, France
| | - Jean-Michel Pawlotsky
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
| | - Christophe Tournigand
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service d'Oncologie Médicale, Créteil, France
| | - Fouad Lafdil
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
- Institut Universitaire de France (IUF), Paris, France
| | - Valérie Paradis
- Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, Service d'Anatomo-Pathologie, Clichy, France
- Université de Paris, Centre de recherche sur l'inflammation, Inserm, U1149, CNRS, ERL8252, Paris, France
| | - Julien Calderaro
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France.
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Département de Pathologie, Créteil, France
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Tang YY, Zhao YN, Zhang T, Chen ZY, Ma XL. Comprehensive radiomics nomogram for predicting survival of patients with combined hepatocellular carcinoma and cholangiocarcinoma. World J Gastroenterol 2021; 27:7173-7189. [PMID: 34887636 PMCID: PMC8613648 DOI: 10.3748/wjg.v27.i41.7173] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 06/26/2021] [Accepted: 09/03/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (cHCC-CCA) is defined as a single nodule showing differentiation into HCC and intrahepatic cholangiocarcinoma and has a poor prognosis. AIM To develop a radiomics nomogram for predicting post-resection survival of patients with cHCC-CCA. METHODS Patients with pathologically diagnosed cHCC-CCA were randomly divided into training and validation sets. Radiomics features were extracted from portal venous phase computed tomography (CT) images using the least absolute shrinkage and selection operator Cox regression and random forest analysis. A nomogram integrating the radiomics score and clinical factors was developed using univariate analysis and multivariate Cox regression. Nomogram performance was assessed in terms of the C-index as well as calibration, decision, and survival curves. RESULTS CT and clinical data of 118 patients were included in the study. The radiomics score, vascular invasion, anatomical resection, total bilirubin level, and satellite lesions were found to be independent predictors of overall survival (OS) and were therefore included in an integrative nomogram. The nomogram was more strongly associated with OS (hazard ratio: 8.155, 95% confidence interval: 4.498-14.785, P < 0.001) than a model based on the radiomics score or only clinical factors. The area under the curve values for 1-year and 3-year OS in the training set were 0.878 and 0.875, respectively. Patients stratified as being at high risk of poor prognosis showed a significantly shorter median OS than those stratified as being at low risk (6.1 vs 81.6 mo, P < 0.001). CONCLUSION This nomogram may predict survival of cHCC-CCA patients after hepatectomy and therefore help identify those more likely to benefit from surgery.
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Affiliation(s)
- You-Yin Tang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yu-Nuo Zhao
- Department of Biotherapy, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, West China Hospital, Chengdu 610041, Sichuan Province, China
| | - Tao Zhang
- West China School of Medicine of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Zhe-Yu Chen
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xue-Lei Ma
- Department of Biotherapy, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, West China Hospital, Chengdu 610041, Sichuan Province, China
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Wang J, Li Z, Liao Y, Li J, Dong H, Peng H, Xu W, Fan Z, Gao F, Liu C, Liu D, Zhang Y. Prediction of Survival and Analysis of Prognostic Factors for Patients With Combined Hepatocellular Carcinoma and Cholangiocarcinoma: A Population-Based Study. Front Oncol 2021; 11:686972. [PMID: 34336671 PMCID: PMC8322675 DOI: 10.3389/fonc.2021.686972] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Accepted: 06/28/2021] [Indexed: 12/18/2022] Open
Abstract
Background Combined hepatocellular carcinoma and cholangiocarcinoma (CHC) is an uncommon subtype of primary liver cancer. Because of limited epidemiological data, prognostic risk factors and therapeutic strategies for patients with CHC tend to be individualized. This study aimed to identify independent prognostic factors and develop a nomogram-based model for predicting the overall survival (OS) of patients with CHC. Methods We recruited eligible individuals from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 and randomly divided them into the training or verification cohort. Univariate and multivariate analyses were performed to identify independent variables associated with OS. Based on multivariate analysis, the nomogram was established, and its prediction performance was evaluated using the consistency index (C-index) and calibration curve. Results In total, 271 patients with CHC were included in our study. The median OS was 14 months, and the 1-, 3-, and 5-year OS rates were 52.3%, 27.1%, and 23.3%, respectively. In the training cohort, multivariate analysis showed that the pathological grade (hazard ratio [HR], 1.26; 95% confidence interval [CI]: 0.96–1.66), TNM stage (HR, 1.21; 95% CI: 1.02 - 1.44), and surgery (HR, 0.26; 95% CI: 0.17 - 0.40) were independent indicators of OS. The nomogram-based model related C-indexes were 0.76 (95% CI: 0.72 - 0.81) and 0.72 (95% CI: 0.66 - 0.79) in the training and validation cohorts, respectively. The calibration of the nomogram showed good consistency of 1-, 3-, and 5-year OS rates between the actual observed survival and predicted survival in both cohorts. The TNM stage (HR, 1.23; 95% CI: 1.01 - 1.49), and M stage (HR, 1.87; 95% CI: 1.14 3.05) were risk factors in the surgical treatment group. Surgical resection and liver transplantation could significantly prolong the survival, with no statistical difference observed. Conclusions The pathological grade, TNM stage, and surgery were independent prognostic factors for patients with CHC. We developed a nomogram model, in the form of a static nomogram or an online calculator, for predicting the OS of patients with CHC, with a good predictive performance.
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Affiliation(s)
- Jitao Wang
- School of Medicine, Southeast University, Nanjing, China.,Xingtai Institute of Cancer Control, Xingtai People's Hospital, Xingtai, China
| | - Zhi Li
- Department of Infection Management, Xingtai General Hospital of North China Healthcare Group, Xingtai, China
| | - Yong Liao
- Xingtai Institute of Cancer Control, Xingtai People's Hospital, Xingtai, China
| | - Jinlong Li
- Xingtai Institute of Cancer Control, Xingtai People's Hospital, Xingtai, China
| | - Hui Dong
- School of Medicine, Southeast University, Nanjing, China
| | - Hao Peng
- School of Medicine, Southeast University, Nanjing, China
| | - Wenjing Xu
- School of Medicine, Southeast University, Nanjing, China
| | - Zhe Fan
- School of Medicine, Southeast University, Nanjing, China
| | - Fengxiao Gao
- Xingtai Institute of Cancer Control, Xingtai People's Hospital, Xingtai, China
| | - Chengyu Liu
- Xingtai Institute of Cancer Control, Xingtai People's Hospital, Xingtai, China
| | - Dengxiang Liu
- Xingtai Institute of Cancer Control, Xingtai People's Hospital, Xingtai, China
| | - Yewei Zhang
- School of Medicine, Southeast University, Nanjing, China.,Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Chen PD, Chen LJ, Chang YJ, Chang YJ. Long-Term Survival of Combined Hepatocellular-Cholangiocarcinoma: A Nationwide Study. Oncologist 2021; 26:e1774-e1785. [PMID: 34213048 DOI: 10.1002/onco.13893] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 06/18/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Combined hepatocellular-cholangiocarcinoma (HCC-CC) is an aggressive primary liver cancer. However, the clinical features are not clearly understood because of limited literature and the complex nature of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). METHODS The records of 100,754 patients with newly diagnosed liver cancer between 2004 and 2013 were obtained from the Taiwan Cancer Registry. The primary outcome measures were overall survival and local recurrence-free survival. The median follow-up time was 60 months (29-120 months). RESULTS HCC-CC tended to share some characteristics with HCC, including increased frequency of stage I cases, high individual tumor rates, and similar patterns of viral hepatitis B and hepatitis C infections. In contrast, HCC-CC showed malignant behavior similar to that of CC, as high-grade tumor cell differentiation and presentation of jaundice were predominant in HCC-CC and CC compared with HCC. Overall survival and local recurrence-free survival rates of HCC-CC were between HCC and CC rates. The mortality rate of HCC-CC was 79.2% (HCC, 77.5%; CC, 93.5%) and the local recurrence rate of HCC-CC was 65.3% (HCC, 74.6%; CC, 88.4%). Surgical treatment was an independent factor for the long-term prognosis of HCC-CC, whereas transarterial chemoembolization (TAcE) promoted survival in both surgical and nonsurgical groups. CONCLUSION Our data confirmed that, although it reflects the malignant behavior of CC, HCC-CC should mainly be characterized as a subtype of HCC. With careful selection of patients, curative resection and TAcE might benefit the survival of patients with HCC-CC. IMPLICATIONS FOR PRACTICE Combined hepatocellular-cholangiocarcinoma (HCC-CC) is a rare cancer that shares demographic characteristics, as well as survival probabilities, with both hepatocellular carcinoma and cholangiocarcinoma. It occurs frequently in patients with hepatitis B virus infection, cirrhotic liver background, and early-stage disease. Compared with 20% of initial resection rates of its counterparts, HCC-CC has higher initial resection rate (55%). Although short-term overall survival is inferior to HCC, its long-term overall survival is similar with HCC.
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Affiliation(s)
- Po-Da Chen
- Department of Surgery, National Taiwan University and Hospital, Taipei, Taiwan.,Department of Surgical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan
| | - Li-Ju Chen
- University of Taipei, Taipei, Taiwan.,Department of Ophthalmology, HepingFuyou Branch, Taipei City Hospital, Taipei, Taiwan
| | - Yao-Jen Chang
- Department of Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.,School of Medicine, Buddhist Tzu Chi University, Hualien, Taiwan
| | - Yun-Jau Chang
- Department of Surgery, National Taiwan University and Hospital, Taipei, Taiwan.,Department of General Surgery, Zhong-Xing Branch, Taipei City Hospital, Taipei, Taiwan
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35
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Kim M, Hwang S, Song GW, Ahn CS, Moon DB, Jung DH, Park GC, Lee SG. Salvage living donor liver transplantation for post-resection recurrence of combined hepatocellular carcinoma-cholangiocarcinoma. KOREAN JOURNAL OF TRANSPLANTATION 2021; 35:116-123. [PMID: 35769525 PMCID: PMC9235333 DOI: 10.4285/kjt.20.0037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 11/19/2020] [Accepted: 11/20/2020] [Indexed: 11/18/2022] Open
Abstract
Salvage liver transplantation (LT) is a definite treatment for recurrent hepatocellular carcinoma (HCC) after hepatectomy. Combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CC) is not eligibly indicated for LT because of high post-transplant recurrence. We present a case of salvage living donor liver transplantation (LDLT) in a patient with tumor recurrence after surgical resection of cHCC-CC. A 61-year-old male patient diagnosed with chronic hepatitis B underwent right posterior sectionectomy for HCC. The pathological diagnosis revealed presence of a 3.2-cm-sized cHCC-CC with stem cell features and intermediate cell-subtype. Intrahepatic tumor recurrence occurred 9 months later and transarterial chemoembolization was performed. Due to the progress of recurrent tumors, ABO-incompatible LDLT was performed. The explant liver pathology revealed four small masses of cHCC-CC with stem cell features. Pulmonary metastasectomy and chest wall resection were performed for metastatic lesions at 10 months after LT. Multiple tumor recurrence was detected at 21 months after LT with progression despite sorafenib administration. Currently, the patient is alive for past 26 months after LT. In conclusion, the clinical sequences of this case suggest that the role of salvage LT for cHCC-CC is much more limited than that for HCC because the tumor biology of cHCC-CC is more aggressive compared with HCC.
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Affiliation(s)
- Minjae Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Shin Hwang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gi-Won Song
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chul-Soo Ahn
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Deok-Bog Moon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Hwan Jung
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gil-Chun Park
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Gyu Lee
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Su YL, Ng CT, Jan YH, Hsieh YL, Wu CL, Tan KT. Remarkable Response to Olaparib in a Patient with Combined Hepatocellular-Cholangiocarcinoma Harboring a Biallelic BRCA2 Mutation. Onco Targets Ther 2021; 14:3895-3901. [PMID: 34234458 PMCID: PMC8254587 DOI: 10.2147/ott.s317514] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Accepted: 06/17/2021] [Indexed: 12/27/2022] Open
Abstract
Combined hepatocellular cholangiocarcinoma (cHCC-CC) is a rare subtype of primary liver malignancy characterized by aggressive behavior and poor prognosis. Radial surgical resection is the standard curative treatment. However, effective therapeutic options for recurrent or metastatic cHCC-CC are still lacking, mainly because of an insufficient understanding of the molecular and genomic alterations of cHCC-CC, preventing the discovery of specialized targeting therapy. Here, we present the case of a patient with metastatic cHCC-CC on first-line treatment of gemcitabine, cisplatin, and nab-paclitaxel. A comprehensive genomic profile revealed four clinically relevant single nucleotide variants (BRCA2, PIK3C2G, RET, and TP53), two amplified genomic regions (CRKL and MAPK1), and 11 heterozygous genomic deletions (BAP1, CDKN2A, PTCH1, TSC1, BRCA2, RB1, RAD51, PALB2, TSC2, SMAD4, and STK11). The patient underwent olaparib treatment and achieved a remarkable and sustained tumor response. Our experience indicates that BRCA2 mutations could be a potential therapeutic target for patients with cHCC-CC.
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Affiliation(s)
- Yu-Li Su
- Division of Hematology Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.,Clinical Trial Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Ca Tung Ng
- ACT Genomics Co., Ltd, Taipei City, Taiwan
| | - Yi-Hua Jan
- ACT Genomics Co., Ltd, Taipei City, Taiwan
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Yu J, Zhang X, Huang Q, Tan S, Xiong X, Gou H. Rare DNA Mismatch Repair-Related Protein Loss in Patients with Intrahepatic Cholangiocarcinoma and Combined Hepatocellular-Cholangiocarcinoma and Their Response to Immunotherapy. Cancer Manag Res 2021; 13:4283-4290. [PMID: 34113169 PMCID: PMC8183674 DOI: 10.2147/cmar.s304281] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 05/11/2021] [Indexed: 02/05/2023] Open
Abstract
Purpose The patients with advanced mismatch repair deficiency (dMMR) cancers can benefit from programmed cell death 1 (PD-1) pathway blockade, regardless of the tumor type. Little is known about the prevalence of dMMR in intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (cHCC-CC). This study aimed to assess the mismatch repair (MMR)-related protein expression in patients with ICC and cHCC-CC. Patients and Methods Formalin-fixed, paraffin-embedded tumor specimens were obtained from patients undergoing surgery at the West china Hospital between 2009 and 2017. The immunoreactions for MLH1, MSH2, MSH6, and PMS2 were investigated to determine the MMR status. Results A total of 97 patients were evaluated, including 73 ICC patients and 24 cHCC-CC patients. The prevalence of dMMR was only found in two cases of 97 patients (2.06%). Both patients are ICC. In 24 cHCC-CC patients, no dMMR was observed. They did not receive an adjuvant chemotherapy after surgery. At the end of the follow-up, one patient was in a tumor-free state, and the other patient had local recurrence and metastasis. After receiving sintilimumab (an immune checkpoint inhibitor [ICI] for PD- 1), the patient had a partial response. Conclusion DMMR was detected in few patients with ICC and cHCC-CC. Thus, it is not recommended to routinely evaluate the MMR status of patients with ICC or cHCC-CC after surgery, but that of patients with advanced ICC or cHCC-CC should be assessed.
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Affiliation(s)
- Jing Yu
- Department of Abdominal Cancer, West China Medical School, Cancer Center, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Xi Zhang
- Department of Abdominal Cancer, West China Medical School, Cancer Center, West China Hospital, Sichuan University, Chengdu, People's Republic of China.,Department of Radiotherapy, The Affiliated Hospital of Hebei University, Baoding, 07100, People's Republic of China
| | - Qiyue Huang
- Department of Abdominal Cancer, West China Medical School, Cancer Center, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Sirui Tan
- Department of Abdominal Cancer, West China Medical School, Cancer Center, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Xianze Xiong
- Department of Bile Duct Surgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Hongfeng Gou
- Department of Abdominal Cancer, West China Medical School, Cancer Center, West China Hospital, Sichuan University, Chengdu, People's Republic of China
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38
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Kim M, Hwang S, Ahn CS, Kim KH, Moon DB, Ha TY, Song GW, Jung DH, Park GC, Hong SM. Postresection prognosis of combined hepatocellular carcinoma-cholangiocarcinoma according to the 2010 World Health Organization classification: single-center experience of 168 patients. Ann Surg Treat Res 2021; 100:260-269. [PMID: 34012943 PMCID: PMC8103158 DOI: 10.4174/astr.2021.100.5.260] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 01/21/2021] [Accepted: 02/16/2021] [Indexed: 12/13/2022] Open
Abstract
Purpose Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) has wide histologic diversity. This study investigated the effects of cHCC-CC histology, according to the 2010 World Health Organization (WHO) classification, on patient prognosis. Methods The medical records of patients who underwent surgical resection for cHCC-CC at our institution between July 2012 and June 2019 were retrospectively evaluated. Results During the study period, 168 patients, 122 males (72.6%) and 46 females (27.4%), underwent surgical resection for cHCC-CC, including 159 patients (94.6%) who underwent R0 resection. Mean tumor diameter was 4.4 ± 2.8 cm, and 161 patients (95.8%) had solitary tumors. Histologically, 86 patients (51.2%) had classical type, and 82 (48.8%) had tumors with stem cell (SC) features, including 33 (19.6%) with intermediate-cell and 23 (13.7%) each with typical SC and cholangiolocellular features; 3 tumors (1.8%) were unclassifiable. At 1, 3, and 5 years, tumor recurrence rates were 31.9%, 49.6%, and 58.1%, respectively, and patient survival rates were 91.0%, 70.2%, and 60.3%, respectively. Univariate analysis showed that tumor size of >5 cm, microscopic and macroscopic vascular invasion, lymph node metastasis, 8th edition of the American Joint Committee on Cancer (AJCC) tumor stage, and 2010 WHO classification were significantly prognostic. Multivariate analysis showed that the 8th AJCC tumor stage and 2010 WHO histologic classification were independently prognostic for tumor recurrence and patient survival. There were no significant prognostic differences among the 3 SC subtypes. Conclusion Postresection outcomes are better in patients with SC-type than with classical-type cHCC-CC.
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Affiliation(s)
- Minjae Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chul-Soo Ahn
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ki-Hun Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Deok-Bog Moon
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae-Yong Ha
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gi-Won Song
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Hwan Jung
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gil-Chun Park
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Cen W, Li J, Tong C, Zhang W, Zhao Y, Lu B, Yu J. Intrahepatic Cholangiocarcinoma Cells Promote Epithelial-mesenchymal Transition of Hepatocellular Carcinoma Cells by Secreting LAMC2. J Cancer 2021; 12:3448-3457. [PMID: 33995623 PMCID: PMC8120174 DOI: 10.7150/jca.55627] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Accepted: 03/19/2021] [Indexed: 12/13/2022] Open
Abstract
Hepatocellular carcinoma and intrahepatic cholangiocarcinoma cells are common primary hepatic tumor cells in the liver. Combined hepatocellular cholangiocarcinoma (CHC) contains both hepatocellular carcinoma cells and intrahepatic cholangiocarcinoma cells in one tumor lesion and these tumors show poor prognosis. Here we examined the potential interaction between hepatocellular carcinoma cells and intrahepatic cholangiocarcinoma cells using cell culture studies. The results showed that culture supernatant from intrahepatic cholangiocarcinoma cells induced endothelial-mesenchymal transition and facilitated the migration and invasion of hepatocellular carcinoma cells, although it did not accelerate the proliferation of hepatocellular carcinoma cells. Furthermore, culture supernatant from intrahepatic cholangiocarcinoma cells increased the chemoresistance of hepatocellular carcinoma cells. Laminin subunit gamma 2 (LAMC2) was detected in the culture supernatant of intrahepatic cholangiocarcinoma cells but not in that of hepatocellular carcinoma cells. Using established LAMC2 knockout intrahepatic cholangiocarcinoma cells, our results demonstrated that intrahepatic cholangiocarcinoma cells promoted the epithelial-mesenchymal transition of hepatocellular carcinoma cells through secreting LAMC2. Our results have revealed a novel mechanism of interaction between intrahepatic cholangiocarcinoma cells and hepatocellular carcinoma cells, which may provide new insight into developing effective treatments for CHC.
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Affiliation(s)
- Wenda Cen
- Shaoxing University School of Medicine, Shaoxing, China
| | - Jiandong Li
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Shaoxing University, Shaoxing, China.,Department of Hepatobiliary Surgery, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, China
| | - Chenhao Tong
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Shaoxing University, Shaoxing, China.,Department of Hepatobiliary Surgery, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, China
| | - Weiguang Zhang
- Department of Molecular Medicine and Clinical Laboratory, Shaoxing Second Hospital, Shaoxing, China
| | - Yunfeng Zhao
- Department of Pharmacology, Toxicology & Neurosciences, LSU Health Sciences Center, Shreveport, LA, USA
| | - Baochun Lu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Shaoxing University, Shaoxing, China.,Department of Hepatobiliary Surgery, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, China
| | - Jianhua Yu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Shaoxing University, Shaoxing, China.,Department of Hepatobiliary Surgery, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, China
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Yen CC, Yen CJ, Shan YS, Lin YJ, Liu IT, Huang HY, Yeh MM, Chan SH, Tsai HW. Comparing the clinicopathological characteristics of combined hepatocellular-cholangiocarcinoma with those of other primary liver cancers by use of the updated World Health Organization classification. Histopathology 2021; 79:556-572. [PMID: 33837585 DOI: 10.1111/his.14384] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 03/26/2021] [Accepted: 04/08/2021] [Indexed: 11/29/2022]
Abstract
AIMS Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is an uncommon hepatic malignancy with a poor outcome. The 2019 World Health Organization (WHO) classification modified the definition and discarded the subtypes with stem cell features. However, the differences among cHCC-CCA, hepatocellular carcinoma (HCC), HCC with stem cell/progenitor features (HCCscf) and intrahepatic cholangiocarcinoma (iCCA) remain undetermined. The aim of this study was to investigate the characteristics of cHCC-CCA in comparison with those of other primary liver cancers by utilising the updated WHO classification. METHODS AND RESULTS We retrospectively analysed 64 cHCC-CCA patients and 55 HCCscf patients from December 2007 to May 2018. Propensity score matching was conducted to compare these with HCC and iCCA patients. Clinicopathological characteristics, event-free survival and overall survival were evaluated with multivariate Cox proportional hazard regression. During a median follow-up of 55.9 months, cHCC-CCA patients had significantly poorer survival than HCCscf patients, and survival intermediate between that of HCC patients and that of iCCA patients. Hepatitis B virus (HBV) infection and high levels of tumour-infiltrating lymphocytes (TILs) were associated with favourable survival in cHCC-CCA patients. In the multivariate analysis, poor hepatic reserve, absence of HBV infection, stage IV disease and low levels of TILs were significant negative prognostic factors in cHCC-CCA patients. After being pooled with other primary liver cancers, cHCC-CCA and iCCA resulted in the worse survival. CONCLUSIONS cHCC-CCA patients have survival intermediate between that of HCC patients and iCCA patients, and HBV infection and high levels of TILs predict favourable survival. Our study provides clinical correlations for the new 2019 WHO classification.
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Affiliation(s)
- Chih-Chieh Yen
- Division of Haematology/Oncology, Department of Internal Medicine, National Cheng Kung University Hospital DouLiuo Branch, Yunlin, Taiwan.,Institute of Clinical Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Chia-Jui Yen
- Department of Oncology, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Yan-Shen Shan
- Department of Surgery, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Yih-Jyh Lin
- Department of Surgery, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - I-Ting Liu
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan.,Department of Oncology, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Hsuan-Yi Huang
- Division of Colorectal Surgery, Department of Surgery, Chi Mei Medical Centre, Tainan, Taiwan
| | - Matthew M Yeh
- Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA.,Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA
| | - Shih-Huang Chan
- Department of Statistics, College of Management, National Cheng Kung University, Tainan, Taiwan
| | - Hung-Wen Tsai
- Department of Pathology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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Kim M, Hwang S, Ahn CS, Kim KH, Moon DB, Song GW, Jung DH, Hong SM. Post-resection prognosis of combined hepatocellular carcinoma-cholangiocarcinoma cannot be predicted by the 2019 World Health Organization classification. Asian J Surg 2021; 44:1389-1395. [PMID: 33766528 DOI: 10.1016/j.asjsur.2021.03.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 03/07/2021] [Accepted: 03/10/2021] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CCA) has wide histologic diversity. This study investigated the prognostic impacts of cHCC-CCA histology according to the 2019 World Health Organization (WHO) classification. METHODS This retrospective observational study included 153 patients who underwent surgical resection for cHCC-CCA at Asan Medical Center between August 2012 and July 2019. RESULTS During the study period, 153 patients, 112 (73.2%) men and 41 (26.8%) women with a mean age of 56.4 ± 10.8 years, underwent R0 resection for cHCC-CCA. Mean tumor diameter was 4.2 ± 2.6 cm, and 147 (96.1%) patients had solitary tumors. According to 2019 WHO classification, 111 (72.5%) patients had cHCC-CCA alone, and 29 of them (26.1%) showed stem cell features. cHCC-CCA-intermediate cell carcinoma and cHCC-CCA-cholangiolocellular carcinoma were identified in 27 (17.6%) and 15 (9.8%), respectively. The 1-, 3-, and 5-year tumor recurrence and patient survival rates were 31.8% and 92.1%, 49.8% and 70.9%, and 59.0% and 61.7%, respectively. Univariate analyses revealed that significant prognostic factors were tumor size >5 cm, microscopic and macroscopic vascular invasion, lymph node metastasis, 8th American Joint Committee on Cancer (AJCC) tumor stage, and status of stem cell features. Multivariate analysis revealed 8th AJCC tumor stage and status of stem cell features as independent prognostic factors. 2019 WHO classification was not associated with post-resection prognosis. CONCLUSIONS 2019 WHO classification was not associated with post-resection prognosis, thus was considered as simplified histologic classification requiring prognostic validation. We suggest that stem cell features should be included as an essential component of the pathology report for cHCC-CCA.
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Affiliation(s)
- Minjae Kim
- Department of Surgery and Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
| | - Shin Hwang
- Department of Surgery and Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
| | - Chul-Soo Ahn
- Department of Surgery and Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
| | - Ki-Hun Kim
- Department of Surgery and Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
| | - Deok-Bog Moon
- Department of Surgery and Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
| | - Gi-Won Song
- Department of Surgery and Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
| | - Dong-Hwan Jung
- Department of Surgery and Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
| | - Seung-Mo Hong
- Department of Surgery and Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
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Jaradat D, Bagias G, Lorf T, Tokat Y, Obed A, Oezcelik A. Liver transplantation for combined hepatocellular-cholangiocarcinoma: Outcomes and prognostic factors for mortality. A multicenter analysis. Clin Transplant 2021; 35:e14094. [PMID: 32970878 DOI: 10.1111/ctr.14094] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 08/06/2020] [Accepted: 09/07/2020] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Combined hepatocellular-cholangiocarcinoma is rare and comprises features of hepatocellular carcinoma and cholangiocarcinoma. The treatment of choice has not yet been defined. The aim of the study was to analyze outcomes of patients with combined hepatocellular-cholangiocarcinoma, who underwent liver transplantation. MATERIAL AND METHODS All patients with combined hepatocellular-cholangiocarcinoma, who underwent liver transplantation, from January 2001 to August 2018 were identified. Pre-, intra- and postoperative data were retrospectively assessed. A univariate analysis was performed to identify prognostic factors. RESULTS A total number of 19 patients were included to this study. Perioperative death was seen in two patients (10.5%). Recurrent disease was reported in 11 patients (64.7%) within the median time of 4 months. One and three years survival rates were 57.1% (CI 0.301-1) and 38.1% (CI 0.137-1). Factors associated mortality were tumor size >3 cm, presence of lymphatic invasion, and prolonged ICU stay. Patients with mixed HCC-CC lesions have significantly better survival compared to patients with separate lesions of HCC and CCC in one liver (p = .025). CONCLUSION Although overall survival rates are clearly decreased compared to HCC patients, liver transplantation should be taken under consideration for selected patients with early stage and real mixed HCC-CC, who are likely to benefit from liver transplantation.
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Affiliation(s)
- Derar Jaradat
- Department of General, Visceral and Transplantation Surgery, University Hospital of Essen, Essen, Germany
| | - Georgios Bagias
- Department of General, Visceral and Transplantation Surgery, University Hospital of Essen, Essen, Germany
| | - Thomas Lorf
- Department of Surgery, University of Göttingen, Göttingen, Germany
| | - Yaman Tokat
- Department of General and Transplantation Surgery, Florence Nightingale Hospital, University Hospital of Istanbul Bilim University, Istanbul, Turkey
| | - Aiman Obed
- Department of Hepatobiliary and Organ Transplant Surgery, Hospital Jordan, Amman, Jordan
| | - Arzu Oezcelik
- Department of General, Visceral and Transplantation Surgery, University Hospital of Essen, Essen, Germany
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Clinical features and outcomes of combined hepatocellular carcinoma and cholangiocarcinoma versus hepatocellular carcinoma versus cholangiocarcinoma after surgical resection: a propensity score matching analysis. BMC Gastroenterol 2021; 21:20. [PMID: 33413162 PMCID: PMC7788698 DOI: 10.1186/s12876-020-01586-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 12/16/2020] [Indexed: 02/06/2023] Open
Abstract
Background Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an infrequent type of primary liver cancer that comprises hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). This study investigated the clinicopathological features and prognosis among cHCC-CC, HCC, and CC groups. Methods We prospectively collected the data of 608 patients who underwent surgical resection for liver cancer between 2011 and 2018 at E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. Overall, 505 patients with cHCC-CC, HCC, and CC were included, and their clinicopathological features, overall survival (OS), and recurrence were recorded. OS and recurrence rates were analyzed using the Kaplan–Meier analysis. Results In the entire cohort, the median age was 61 years and 80% were men. Thirty-five (7.0%) had cHCC-CC, 419 (82.9%) had HCC, and 51 (10.1%) had CC. The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. OS was significantly lower in the cHCC-CC group than in the HCC group but was not significantly higher in the cHCC-CC group than in the CC group. The median OS of cHCC-CC, HCC, and CC groups was 50.1 months [95% confidence interval (CI): 38.7–61.2], 62.3 months (CI: 42.1–72.9), and 36.2 months (CI: 15.4–56.5), respectively. Cumulative OS rates at 1, 3, and 5 years in cHCC-CC, HCC, and CC groups were 88.5%, 62.2%, and 44.0%; 91.2%, 76.1%, and 68.0%; and 72.0%, 48.1%, and 34.5%, respectively. After propensity score matching (PSM), OS in the cHCC-CC group was not significantly different from that in the HCC or CC group. However, OS was significantly higher in the HCC group than in the CC group before and after PSM. Furthermore, the disease-free survival was not significantly different among cHCC-CC, HCC, and CC groups before and after PSM. Conclusion The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. The OS rate was significantly lower in the cHCC-CC group than the HCC group. However, after PSM, OS and disease-free survival in the cHCC-CC group were not significantly different from those in the HCC or CC group.
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Tang Y, Wang L, Teng F, Zhang T, Zhao Y, Chen Z. The clinical characteristics and prognostic factors of combined Hepatocellular Carcinoma and Cholangiocarcinoma, Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma after Surgical Resection: A propensity score matching analysis. Int J Med Sci 2021; 18:187-198. [PMID: 33390787 PMCID: PMC7738961 DOI: 10.7150/ijms.50883] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 10/13/2020] [Indexed: 02/05/2023] Open
Abstract
Background: Clinical characteristics and prognosis among combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (cHCC-CC) with HCC and intrahepatic cholangiocarcinoma (ICC) were inconsistent in previous studies. The aim of this study was to compare postoperative prognosis among cHCC-CC, HCC and ICC, and investigated the prognostic risk factor of cHCC-CC after surgical resection. Methods: A total of 1041 eligible patients with pathological diagnosis of cHCC-CC (n=135), HCC (n=698) and ICC (n=208) were enrolled in this study. Univariate and multivariate Cox analysis were applied for assessing important risk factors. cHCC-CC were further 1:1 matched with HCC and ICC on important clinical risk factors. Survival curves of matched and unmatched cohorts were depicted by Kaplan-Meier method with log-rank test. Results: Patients with cHCC-CC had similar rate of sex, age and cirrhosis with HCC (p<0.05) and comparable incidence of hepatitis B or C with ICC (p=0.197). Patients of cHCC-CC had intermediate prognosis between HCC and ICC, with median overall survival (OS) time of cHCC-CC, HCC and ICC of 20.5 months, 35.7 months and 11.6 months (p<0.001). In matched cohorts, the OS of cHCC-CC were worse than HCC (p<0.001) but comparable with ICC (p=0.06), while the disease-free survival (DFS) of cHCC-CC was worse than HCC but better than ICC (p<0.05). And lymph node infiltration and postoperative transarterial chemoembolization (TACE) were independent risk factors of cHCC-CC associated with prognosis. Conclusion: The long term survival of cHCC-CC was worse than HCC but comparable with ICC when matched on albumin level, tumor size, lymph node infiltration, tumor stage and margin. Presence of lymph node infiltration and no postoperative TACE were associated with poor prognosis of cHCC-CC.
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Affiliation(s)
- Youyin Tang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, P.R. China
| | - Lingyan Wang
- Department of Obstetrics and Gynecology Nursing, Key Laboratory of Birth Defects and Related Disease of Women and Children, West China Second University Hospital, Sichuan University, No. 20 South Renmin Road, Chengdu 610041, P.R. China
| | - Fei Teng
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, P.R. China
| | - Tao Zhang
- Department of Biotherapy, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, P.R. China
| | - Yunuo Zhao
- Department of Biotherapy, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, P.R. China
| | - Zheyu Chen
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, P.R. China
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Torbenson MS. Hepatocellular carcinoma: making sense of morphological heterogeneity, growth patterns, and subtypes. Hum Pathol 2020; 112:86-101. [PMID: 33387587 DOI: 10.1016/j.humpath.2020.12.009] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 12/18/2020] [Accepted: 12/21/2020] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinomas are not a homogenous group of tumors but have multiple layers of heterogeneity. This heterogeneity has been studied for many years with the goal to individualize care for patients and has led to the identification of numerous hepatocellular carcinoma subtypes, defined by morphology and or molecular methods. This article reviews both gross and histological levels of heterogeneity within hepatocellular carcinoma, with a focus on histological findings, reviewing how different levels of histological heterogeneity are used as building blocks to construct morphological hepatocellular carcinoma subtypes. The current best practice for defining a morphological subtype is outlined. Then, the definition for thirteen distinct hepatocellular carcinoma subtypes is reviewed. For each of these subtypes, unresolved issues regarding their definitions are highlighted, including recommendations for these problematic areas. Finally, three methods for improving the research on hepatocellular carcinoma subtypes are proposed: (1) Use a systemic, rigorous approach for defining hepatocellular carcinoma subtypes (four-point model); (2) Once definitions for a subtype are established, it should be followed in research studies, as this common denominator enhances the ability to compare results between studies; and (3) Studies of subtypes will be more effective when morphological and molecular results are used in synergistic and iterative study designs where the results of one approach are used to refine and sharpen the results of the other. These and related efforts to better understand heterogeneity within hepatocellular carcinoma are the most promising avenue for improving patient care by individualizing patient care.
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Affiliation(s)
- Michael S Torbenson
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA.
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Elevated neutrophil-to-lymphocyte ratio and predominance of intrahepatic cholangiocarcinoma prediction of poor hepatectomy outcomes in patients with combined hepatocellular-cholangiocarcinoma. PLoS One 2020; 15:e0240791. [PMID: 33306714 PMCID: PMC7732129 DOI: 10.1371/journal.pone.0240791] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Accepted: 10/03/2020] [Indexed: 12/29/2022] Open
Abstract
Objectives Although elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with survival in some liver cancers, its prognostic relevance has not been studied in the context of combined hepatocellular cholangiocarcinoma CHCC-CC, a rare primary liver cancer. We investigated whether elevated NLR and a predominance of cholangiocarcinoma might predict poor prognosis in patients with resectable CHCC-CC. Methods We retrospectively reviewed the clinicopathologic data of forty-two patients with CHCC-CC receiving hepatectomies at our hospital. We used Kaplan-Meier and Cox regression to analyze survival. Results Two-year disease-free survival and five-year overall survival rates were 43.2% and 32.9%, respectively. Univariate analyses showed that patients with NLR ≥3 had significantly worse 2-year DFS and 5-year OS rates. Univariant Kaplan-Meier survival analysis also associated these rates with a predominance in intrahepatic cholangiocarcinoma, AJCC tumor stage, pathological T stage and lymph-vascular invasion. However, our multivariate analysis found NLR ≥3 to be the only independent predictor of disease recurrence and poorer survival. Conclusions Neutrophil-to-lymphocyte ratio was the most important independent predictor of poorer survival in patients with resectable CHCC-CC. Predominance of intrahepatic cholangiocarcinoma, advanced AJCC tumor stage and pathological T stage, and lymph-vascular invasion also may affect poor prognosis in patients receiving complete tumor resections.
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Wang T, Wang W, Zhang J, Yang X, Shen S, Wang W. Development and Validation of a Nomogram for Differentiating Combined Hepatocellular Cholangiocarcinoma From Intrahepatic Cholangiocarcinoma. Front Oncol 2020; 10:598433. [PMID: 33363028 PMCID: PMC7756117 DOI: 10.3389/fonc.2020.598433] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 11/04/2020] [Indexed: 02/05/2023] Open
Abstract
Objectives To establish a nomogram based on preoperative laboratory study variables using least absolute shrinkage and selection operator (LASSO) regression for differentiating combined hepatocellular cholangiocarcinoma (cHCC) from intrahepatic cholangiocarcinoma (iCCA). Methods We performed a retrospective analysis of iCCA and cHCC patients who underwent liver resection. Blood signatures were established using LASSO regression, and then, the clinical risk factors based on the multivariate logistic regression and blood signatures were combined to establish a nomogram for a differential preoperative diagnosis between iCCA and cHCC. The differential accuracy ability of the nomogram was determined by Harrell’s index (C-index) and decision curve analysis, and the results were validated using a validation set. Furthermore, patients were categorized into two groups according to the optimal cut-off values of the nomogram-based scores, and their survival differences were assessed using Kaplan-Meier curves. Results A total of 587 patients who underwent curative liver resection for iCCA or cHCC between January 2008 and December 2017 at West China Hospital were enrolled in this study. The cHCC score was based on the personalized levels of the seven laboratory study variables. On multivariate logistic analysis, the independent factors for distinguishing cHCC were age, sex, biliary duct stones, and portal hypertension, all of which were incorporated into the nomogram combined with the cHCC-score. The nomogram had a good discriminating capability, with a C-index of 0.796 (95% CI, 0.752–0.840). The calibration plot for distinguishing cHCC from iCCA showed optimal agreement between the nomogram prediction and actual observation in the training and validation sets. The decision curves indicated significant clinical usefulness. Conclusion The nomogram showed good accuracy for the differential diagnosis between iCCA and cHCC preoperatively, and therapeutic decisions would improve if it was applied in clinical practice.
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Affiliation(s)
- Tao Wang
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, China
| | - Wanxiang Wang
- Department of Hepatobiliary, Pancreatic, and Splenic Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Jinfu Zhang
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, China
| | - Xianwei Yang
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, China
| | - Shu Shen
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, China
| | - Wentao Wang
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, China
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Schizas D, Mastoraki A, Routsi E, Papapanou M, Tsapralis D, Vassiliu P, Toutouzas K, Felekouras E. Combined hepatocellular-cholangiocarcinoma: An update on epidemiology, classification, diagnosis and management. Hepatobiliary Pancreat Dis Int 2020; 19:515-523. [PMID: 32753331 DOI: 10.1016/j.hbpd.2020.07.004] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 07/17/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Combined hepatocellular-cholangiocarcinoma (CHC) is a rare subtype of primary hepatic malignancies, with variably reported incidence between 0.4%-14.2% of primary liver cancer cases. This study aimed to systematically review the epidemiological, clinicopathological, diagnostic and therapeutic data for this rare entity. DATA SOURCES We reviewed the literature of diagnostic approach of CHC with special reference to its clinical, molecular and histopathological characteristics. Additional analysis of the recent literature in order to evaluate the results of surgical and systemic treatment of this entity has been accomplished. RESULTS The median age at CHC's diagnosis appears to be between 50 and 75 years. Evaluation of tumor markers [alpha fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA)] along with imaging patterns provides better opportunities for CHC's preoperative diagnosis. Reported clinicopathologic prognostic parameters possibly correlated with increased tumor recurrence and grimmer survival odds include advanced age, tumor size, nodal and distal metastases, vascular and regional organ invasion, multifocality, decreased capsule formation, stem-cell features verification and increased GGT as well as CA19-9 and CEA levels. In case of inoperable or recurrent disease, combinations of cholangiocarcinoma-directed systemic agents display superior results over sorafenib. Liver-directed methods, such as transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI), hepatic arterial infusion chemotherapy (HAIC), radioembolization and ablative therapies, demonstrate inferior efficacy than in cases of hepatocellular carcinoma (HCC) due to CHC's common hypovascularity. CONCLUSIONS CHC demonstrates an overlapping clinical and biological pattern between its malignant ingredients. Natural history of the disease seems to be determined by the predominant tumor element. Gold standard for diagnosis is histology of surgical specimens. Regarding therapeutic interventions, major hepatectomy is acknowledged as the cornerstone of treatment whereas minor hepatectomy and liver transplantation may be applied in patients with advanced cirrhosis. Despite all therapeutic attempts, prognosis of CHC remains dismal.
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Affiliation(s)
- Dimitrios Schizas
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Aikaterini Mastoraki
- Fourth Department of Surgery, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece.
| | - Eleni Routsi
- Fourth Department of Surgery, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - Michail Papapanou
- Fourth Department of Surgery, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | | | - Pantelis Vassiliu
- Fourth Department of Surgery, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - Konstantinos Toutouzas
- First Department of Propaedeutic Surgery, National and Kapodistrian University of Athens, Hippocration Hospital, Athens, Greece
| | - Evangelos Felekouras
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
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Badar W, Van Ha T, Zangan S, Navuluri R, Pillai A, Baker T, Ahmed O. Yttrium-90 Radioembolization Therapy for Combined Hepatocellular and Cholangiocarcinoma. Gastrointest Tumors 2020; 7:144-150. [PMID: 33173778 DOI: 10.1159/000508386] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 04/27/2020] [Indexed: 12/29/2022] Open
Abstract
Purpose To report outcomes of transarterial radioembolization (TARE) using glass microspheres for the treatment of mixed hepatocellular-cholangiocarcinoma (HCC-CC) in a propensity-matched study. Material and Methods Between 2013 and 2019, 10 consecutive patients with histologically confirmed HCC-CC received TARE of a targeted territory using glass microspheres as a primary initial treatment. Baseline demographics in addition to tumor distribution, Child Pugh score, and BCLC were recorded. Tumor response was assessed according to modified RECIST criteria. The HCC-CC cohort was matched to the HCC cohort, and objective response and survival analysis was performed. Results In the HCC-CC cohort, patients had a 70% objective response rate (ORR), and in the HCC cohort, patients had a 90% ORR after matching (p = 0.54). The median overall survival (OS) for HCC patients was 12.3 months (95% CI: 6.0-17.4 months) in the matched population, and for HCC-CC patients, the median OS was 15.2 months (95% CI: 2.7-20.2 months) (p = 0.98). The median progression-free survival (PFS) for HCC patients was 11.6 months (95% CI: 2.53-19.3 months) in the matched population, and for HCC-CC patients, the median PFS was 15.2 months (95% CI: 2.7-20.2 months) (p = 0.94). The median transplant-free survival (TFS) for HCC patients was 12.3 months (95% CI: 6.0-17.4 months) in the matched population, and for HCC-CC patients, the median TFS was 15.2 months (95% CI: 2.7-20.2 months) (p = 0.98). Conclusions While outcomes of combined HCC-CC are poor and optimal treatment remains undefined, TARE appears to represent an effective locoregional treatment with survival outcomes similar to that of HCC treated by TARE.
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Affiliation(s)
- Wali Badar
- Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA
| | - Thuong Van Ha
- Section of Interventional Radiology, University of Chicago, Chicago, Illinois, USA
| | - Steven Zangan
- Section of Interventional Radiology, University of Chicago, Chicago, Illinois, USA
| | - Rakesh Navuluri
- Section of Interventional Radiology, University of Chicago, Chicago, Illinois, USA
| | - Anjana Pillai
- Section of Interventional Radiology, University of Chicago, Chicago, Illinois, USA
| | - Talia Baker
- Section of Interventional Radiology, University of Chicago, Chicago, Illinois, USA
| | - Osman Ahmed
- Section of Interventional Radiology, University of Chicago, Chicago, Illinois, USA
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Peng Y, Lin P, Wu L, Wan D, Zhao Y, Liang L, Ma X, Qin H, Liu Y, Li X, Wang X, He Y, Yang H. Ultrasound-Based Radiomics Analysis for Preoperatively Predicting Different Histopathological Subtypes of Primary Liver Cancer. Front Oncol 2020; 10:1646. [PMID: 33072550 PMCID: PMC7543652 DOI: 10.3389/fonc.2020.01646] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Accepted: 07/27/2020] [Indexed: 12/12/2022] Open
Abstract
Background Preoperative identification of hepatocellular carcinoma (HCC), combined hepatocellular–cholangiocarcinoma (cHCC-ICC), and intrahepatic cholangiocarcinoma (ICC) is essential for treatment decision making. We aimed to use ultrasound-based radiomics analysis to non-invasively distinguish histopathological subtypes of primary liver cancer (PLC) before surgery. Methods We retrospectively analyzed ultrasound images of 668 PLC patients, comprising 531 HCC patients, 48 cHCC-ICC patients, and 89 ICC patients. The boundary of a tumor was manually determined on the largest imaging slice of the ultrasound medicine image by ITK-SNAP software (version 3.8.0), and then, the high-throughput radiomics features were extracted from the obtained region of interest (ROI) of the tumor. The combination of different dimension-reduction technologies and machine learning approaches was used to identify important features and develop the moderate radiomics model. The comprehensive ability of the radiomics model can be evaluated by the area under the receiver operating characteristic curve (AUC). Results After digitally processing tumor ultrasound images, 5,234 high-throughput radiomics features were obtained. We used the Spearman + least absolute shrinkage and selection operator (LASSO) regression method for feature selection and logistics regression for modeling to develop the HCC-vs-non-HCC radiomics model (composed of 16 features). The Spearman + statistical test + random forest methods were used for feature selection, and logistics regression was applied for modeling to develop the ICC-vs-cHCC-ICC radiomics model (composed of 19 features). The overall performance of the radiomics model in identifying different histopathological types of PLC was moderate, with AUC values of 0.854 (training cohort) and 0.775 (test cohort) in the HCC-vs-non-HCC radiomics model and 0.920 (training cohort) and 0.728 (test cohort) in the ICC-vs-cHCC-ICC radiomics model. Conclusion Ultrasound-based radiomics models can help distinguish histopathological subtypes of PLC and provide effective clinical decision making for the accurate diagnosis and treatment of PLC.
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Affiliation(s)
- Yuting Peng
- Department of Medical Ultrasonics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Peng Lin
- Department of Medical Ultrasonics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Linyong Wu
- Department of Medical Ultrasonics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Da Wan
- Department of Medical Ultrasonics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yujia Zhao
- Department of Medical Ultrasonics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Li Liang
- Department of Medical Ultrasonics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xiaoyu Ma
- Department of Medical Ultrasonics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Hui Qin
- Department of Medical Ultrasonics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yichen Liu
- Department of Medical Ultrasonics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xin Li
- GE Healthcare, Shanghai, China
| | | | - Yun He
- Department of Medical Ultrasonics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Hong Yang
- Department of Medical Ultrasonics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
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